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Obesity stands out as one of the most significant health problems in the modern world. The prevalence of high‐calorie diets (HCDs) globally exacerbates this condition. Throughout history, plants and plant‐derived food products have been utilized for medicinal purposes, demonstrating their efficacy in the treatment and prevention of various diseases. Gundelia tournefortii (GT), a plant of interest, is known to possess beneficial properties. Hence, this study aimed to investigate the immunotoxic and neurotoxic effects of two different doses of GT plant extract on the liver, brain, and heart tissues of obese rats. For this purpose, Wistar male rats were divided into four groups: “CG,” “HCDG,” “HCDGUN1,” and “HCDGUN2” At the conclusion of the study, adenosine deaminase (ADA) and myeloperoxidase (MPO) activities, as well as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) biomarkers, were evaluated in the liver, heart, and brain tissues. The study results revealed a statistically significant increase in ADA and MPO activities in the HCDG group compared to the CG group, alongside a significant decrease in the HCDGUN groups compared to the HCDG group. Regarding AChE and BChE activities, a statistically significant decrease was observed in the HCDG group compared to the CG group, whereas an increase was noted in the HCDGUN groups relative to the HCDG group, with the latter approaching values similar to those of the control group. In conclusion, the intake of GT plant extract exhibited positive effects on the immunotoxic and neurotoxic effects induced by HCD in rats with an experimental obesity model, as evidenced by tissue biomarker evaluations. [ABSTRACT FROM AUTHOR]

Background: After the Coronavirus Disease pandemic, depression became more present, including in adolescents. Escitalopram, a selective serotonin reuptake inhibitor, was approved in 2009 for treatment of the major depressive disorder, both in children and adolescents. The undesirable effects of antidepressants on sexual dysfunction are usually underestimated. Aims: To investigate the effects of chronic mild stress, induced from peripuberty up to adulthood, on male sexual behavior parameters, with or without the escitalopram treatment, using rats as experimental model in a translational study. Materials and methods: Forty‐four peripubertal male rats were distributed into four groups: Sham control, escitalopram, stress, and stress + escitalopram. The chronic mild stress consisted of nine different stressors randomly applied one per day, for 8 weeks (from 41 to 97 days postpartum). Escitalopram therapy by gavage (10 mg/kg) started at 70 days postpartum and lasted for 4 weeks. The male sexual behavior parameters were evaluated at 114 days postpartum. After that, euthanasia was performed for blood and testis collection. Histopathology of the testes and plasmatic testosterone level were carried out. Results: There was a reduction in sexual activity and motivation in rats exposed to the stress protocol, which were treated or not with escitalopram, as well as an increase in the total number of mounts in animals exposed to the stress and treated with escitalopram. The testosterone levels were lower in animals exposed to the stress, which were or not treated with escitalopram (stress and stress + escitalopram). The frequency of histologically normal seminiferous tubule sections was lower in animals that were exposed to the stress and/or received escitalopram (escitalopram, stress, and stress + escitalopram). Conclusion: Chronic mild stress induced from peripuberty, associated or not to escitalopram treatment, altered the testosterone levels and testicular histoarchitecture and seems to be related to the reduction in male sexual motivation. [ABSTRACT FROM AUTHOR]

Background: The autonomic nervous system (ANS) is affected by several factors, including major nutrients. However, their effects on the ANS remains unclear. Most studies had several limitations. They focused on humans, therefore they had difficulties excluding factors other than the nutrients. Their observation periods were too short (<4 hours) to align with typical absorption times of carbohydrates versus fats. They assessed the effects compared with the pre-prandial state rather than comparisons between different nutrient types. Objective: We aimed to investigate the effects of carbohydrates and fats on the ANS. Method: We employed a rat model to exclude the effects of external stimuli, used sufficient observation period, and compared the ANS parameters among animals fed 3 different diets. The rats were divided into carbohydrate-rich-diet (carb group) and fat-rich-diet (fat group) groups. We investigated the effects of carbohydrates and fats on the ANS by measuring heart rate variability parameters in rats. Electrodes and electrocardiography (ECG) transmitters were implanted in 14 Wistar rats maintained on a standard diet for 2 days followed by the experimental diets for 2 days. ECG readings were continuously recorded for 4 days. The R waves, function of the R-R interval, and time were calculated. A fast Fourier transform was used to obtain the power spectrum of the fluctuation (low frequency [LF: 0.2-0.75 Hz]; high frequency [HF: 0.75-3.0 Hz]; LF/HF ratio). Result: Compared with the standard-diet group, the carb group showed significantly increased HF activity, while the fat group showed a significantly increased LF/HF ratio. Conclusion: The results reveal a link between macronutrients and ANS activity. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive age leading to infertility. Besides reproductive and hormonal disturbances, PCOS is often characterized by vitamin D3 (VD) deficiency. This study aimed to determine the effect of VD on uterine histoarchitecture, the biochemical composition of gland secretions, and the insulin signal transduction pathway using a PCOS rat model. The experiment was conducted on four animal groups (n=8/group): control (C), VD supplemented (VD; 500 IU/day), letrozole-treated (PCOS; 1 mg/kg body weight), and VD-treated PCOS (PCOS+VD) group. Herein, VD supplementation did not improve histomorphometric parameters in the PCOS uterus, whereas clearly influenced sugar composition in uterine gland secretions, restoring their content to that observed in the C group. Furthermore, we found that VD can reduce peripheral and local uterine insulin resistance developed in the PCOS rats via activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and subsequent glucose metabolism in the uterus. To sum up, the present results suggest a possible beneficial role of VD supplementation for the maintenance of uterus functions in PCOS rats. [ABSTRACT FROM AUTHOR]

The sternohyoid muscle depresses the hyoid bone, but it is unclear whether the muscle contributes to respiratory and swallowing mechanisms. This study aimed to clarify whether the sternohyoid muscle participates in the respiration and swallowing reflex and how the activity is modulated in two conditions: with airway stenosis and with a fixed sternohyoid muscle length. Electromyographic activity in the sternohyoid, digastric, thyrohyoid, and diaphragm muscles was recorded in anesthetized rats. The sternohyoid muscle activity was observed in the inspiratory phase and during swallowing, and was well coordinated with digastric and thyrohyoid muscle activity. With airway stenosis, the respiratory activity per respiratory cycle was facilitated in all assessed muscles but the facilitation of activity per second occurred only in the digastric, thyrohyoid, and sternohyoid muscles. With airway stenosis, the swallowing activity was facilitated only in the digastric muscle but not in the thyrohyoid and sternohyoid muscles. Swallowing activity was not observed in the sternohyoid muscle in the condition with the sternohyoid muscle length fixed, although increased inspiratory activity remained. The current results suggest that 1) the sternohyoid muscle is slightly activated in the inspiratory phase, 2) the effect of airway stenosis on respiratory function may differ between the upper airway muscles and diaphragm, and 3) swallowing activity in the sternohyoid muscle is not dominantly controlled by the swallowing central pattern generator but instead occurs as a myotatic reflex. NEW & NOTEWORTHY: We found that the sternohyoid muscle was activated in the inspiratory phase. However, increased airway resistance had different effects on the extrathoracic muscles than on the diaphragm. The swallowing activity of the sternohyoid disappeared when the muscle length was fixed. These findings suggest that the sternohyoid muscle may be activated not by the swallowing central pattern generator but as a myotatic reflex. [ABSTRACT FROM AUTHOR]

Cataracts are a disease that reduces vision due to opacity formation of the lens. Diabetic cataracts occur at young age and progress relatively quickly, so the development of effective treatment has been awaited. Several studies have shown that pyruvate inhibits oxidative stress and glycation of lens proteins, which contribute to onset of diabetic cataracts. However, detailed molecular mechanisms have not been revealed. In this study, we attempted to reduce galactose‐induced opacity by pyruvate with rat ex vivo model. Rat lenses were extracted and cultured in galactose‐containing medium to induce lens opacity. After opacity had developed, continued culturing with pyruvate in the medium resulted in a reduction of lens opacity. Subsequently, we conducted microarray analysis to investigate the genes that contribute to the therapeutic effect. We performed quantitative expression measurements using RT‐qPCR for extracted genes that were upregulated in cataract‐induced lenses and downregulated in pyruvate‐treated lenses, resulting in the identification of 34 candidate genes. Functional analysis using the STRING database suggests that metallothionein‐related factors (Mt1a, Mt1m, and Mt2A) and epithelial‐mesenchymal transition‐related factors (Acta2, Anxa1, Cd81, Mki67, Timp1, and Tyms) contribute to the therapeutic effect of cataracts. [ABSTRACT FROM AUTHOR]

Radiotherapy (RAD) is a common cancer treatment method, but it can have unintended lung side effects. L-carnitine (LCAR) is an amino acid with antioxidant and anti-inflammatory properties. This study aims to demonstrate the effects of LCAR against radiation-induced acute lung injury and to elucidate its possible protective molecular mechanisms. A total of 32 Wistar albino rats were separated into four groups: control, RAD (10 Gy once on 1st day), RAD + LCAR (intraperitoneally, 200 mg/kg/d, for 10 days), and LCAR. At the end of the experiment, the rats were euthanized, and the lung tissues were collected for histopathological, immunohistochemical, biochemical, and genetic analysis. Emphysema, pronounced hyperemia, increased total oxidant status, and increased caspase-3 and TNF-α immunostainings were all seen in the lung tissues of the RAD group. LCAR treatment reduced these negative effects. In addition, AMPK and SIRT1 gene expressions increased in the RAD + LCAR group compared to the RAD group, while TGF-1ß gene expression decreased. While RAD caused major damage to the lungs of rats, LCAR application reduced this damage through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. Specifically, LCAR reduced fibrosis while attenuating RAD-induced inflammation and oxidative stress via the AMPK/SIRT1/TGF-1ß pathway. Therefore, LCAR can be considered a supplement to reduce complications associated with RAD. [ABSTRACT FROM AUTHOR]

Fracture healing is a process in which many factors interact. In addition to many treatments, physical and biological therapy methods that affect different steps of this process, there are many biological and chemical agents that cause fracture union delay. Although the number of studies on fracture healing is increasing day by day, the mechanism of fracture healing, which is not fully understood, still attracts the attention of all researchers. In this study, we aimed to investigate the effects of favipiravir and hydroxychloroquine used in the treatment of COVID-19. In this study, 48 male Wistar rats weighing 300 ± 50 g were used. Each group was divided into eight subgroups of six rats each to be sacrificed at the 2nd and 4th weeks and evaluated radiologically and histologically. Favipiravir (group 1), hydroxychloroquine (group 2), favipiravir + hydroxychloroquine (group 3), and random control (group 4) were used. A statistically significant difference was observed between the 15th day histological scoring averages of the groups (p < 0.05). Although there was no statistically significant difference between the 15th day radiological score distributions of the groups (p > 0.05), we obtained different results in terms of complete bone union distributions and radiological images of the fracture line. Although favipiravir has a negative effect on fracture union in the early period, favipiravir may have a positive effect on fracture union in the late period. We did not find any effect of hydroxychloroquine on fracture union. [ABSTRACT FROM AUTHOR]

Background/Objectives: In Southeast Asia, the traditional use of young coconut (Cocos nucifera L.) juice (YCJ) by women to alleviate postmenopausal symptoms suggests potential estrogenic properties. However, few studies explore the impact of YCJ on pathologies associated with estrogen deficiency in postmenopausal animal models. This study examines the impact of YCJ supplementation on memory impairment and depression-like behavior in ovariectomized (Ovx) rats. Methods: Ten-week-old female rats underwent either a sham operation (Sham) or bilateral Ovx. The rats in the Ovx + YCJ group received 5×-concentrated YCJ by gavage at a dose of 15 mL/kg body weight. Twelve weeks later, the Morris water maze and forced swim tests were used to evaluate hippocampus-dependent spatial memory and depression-like behavior, respectively. Results: The Ovx rats displayed significant memory impairment (p < 0.05) and depression-like behaviors (p < 0.05), while the memory performance in the rats in the Ovx + YCJ group resembled that of the Sham rats. However, the administration of YCJ did not result in the improvement of depression-like behavior. Conclusions: These findings suggest that YCJ consumption may help ameliorate memory impairment in postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: This longitudinal study examined the early effects of type 1 diabetes on bone mechanical properties and metabolic markers in mature rats, focusing on the natural progression of diabetes-induced changes without external treatments. Methods: Forty-eight 8-month-old male Wistar rats were divided into two groups, with one group receiving a single dose of streptozotocin (STZ, 60 mg/kg). Assessments were performed 2, 4, and 8 weeks post-administration, including serum biochemical analyses, bone marker assessments, and mechanical bone tests. The data were analyzed using two-way ANOVA to evaluate the impact of time and treatment. Results: At 2 weeks, diabetic rats showed increased fasting blood glucose (p < 0.001), decreased insulin levels (p = 0.03), and changes in HOMA markers (p < 0.001), liver enzymes (p < 0.001), inflammatory markers (p < 0.001), and bone metabolism markers (osteocalcin (p < 0.001), OPG (p = 0.006), RANKL (p < 0.001), and OPG/RANKL ratio (p < 0.001)), with initial alterations in bone geometry. By week 4, decreased body weight in the diabetic group (p < 0.001) led to further changes in bone geometry and initial differences in mechanical properties. At 8 weeks, significant declines in body (p < 0.001) and bone (p < 0.001) weights were observed, along with further deterioration in bone geometry and mechanical properties. Conclusions: The study highlights the significant impact of STZ-induced diabetes on bone health as early as two weeks post-STZ administration, with marked temporal changes in biochemical markers and mechanical properties. [ABSTRACT FROM AUTHOR]

The expression of apoptosis, autophagy and necroptosis markers in rat hippocampal cells after long-term intake of excessive fluoride (F–) doses was studied at transcriptional and translational levels. Male Wistar rats were divided into 4 groups given 0.4 (control), 5, 20, and 50 mg/L F– (as NaF) with drinking water over 12 months. Changes in the content of effectors of mitochondrial (Bcl-2, Bax, caspase-9, caspase-3) and receptor (caspase-8, Fas) pathways of apoptosis, mediators (Ulk-1, Beclin-1) and modulators (AMPK, Akt, mTOR) of autophagy, as well as necroptosis effectors (RIP and MLKL), were assessed by immunoblotting, while the expression of Bcl2, Bax, Casp3, Ulk1, Beclin1, Prkaa1, Akt, and mTor genes—by real-time PCR. In the hippocampus of F–-exposed animals, the expression ratio of Bcl2/Bax genes and Bcl-2/Bax proteins decreased, caspase-9 and caspase-3 were activated, but caspase-8 and Fas receptor levels remained stable. Long-term F– intake had no effect on the content of the autophagy initiator Ulk-1 and protein kinases AMPK, Akt and mTOR, but led to the inhibition of the key autophagy mediator Beclin-1. Expression levels of the necroptosis effectors RIP and MLKL in hippocampal cells of rats exposed to excessive F– doses did not change as well. Thus, long-term exposure to excessive F– was accompanied by the activation of apoptosis, mainly through the mitochondrial pathway, against the background of autophagy suppression. [ABSTRACT FROM AUTHOR]

Background: Several studies have shown that obesity alters the function and structure of the heart. Objectives: This study examined the impact of increasing aerobic exercise (IAE) on the mRNA expression of Cyclooxygenase-2 (COX-2) and nuclear factor Kappa B (NF-κB) in the cardiac tissue of rats fed a high-fat diet (HFD). Methods: Twenty-four male Wistar rats were divided into two groups and fed two types of diets for eight weeks: Control and HFD groups. After eight weeks, the rats on the HFD were further divided into HFD and HFD + IAE groups. The exercise program was conducted for six weeks, with five sessions per week, progressing from moderate to high intensity. The program followed the principle of gradual overload and was based on the maximum speed of the rats. The expression of COX-2 and NF-κB genes was assessed. Results: The expression of COX-2 and NF-κB genes increased in the HFD group compared to the control group. After six weeks, the expression of NF-κB and COX-2 genes decreased in the HFD + IAE group compared to the HFD group. Conclusions: Six weeks of IAE appears to reduce the inflammatory process in rats with HFD-induced obesity. [ABSTRACT FROM AUTHOR]

Background: Sweetgum oil has been traditionally used to treat wounds, respiratory tract problems, osteoarthritis and various stomach ailments. In this study, the effects of sweetgum oil on ethanol-induced chronic gastritis in rats were investigated. Methods: Thirty Wistar albino rats were divided into 5 groups. Group 1 served as control and received no treatment. Except for control, all animals received oral doses of 8 g/kg of 56% ethanol twice a week for 4 weeks to induce gastritis. Group 2, the ethanol group received only ethanol. Group 3 was treated with the conventional treatment of 20 mg/kg omeprazole daily for 2 weeks. Group 4 was treated with 150 mg/kg of sweetgum oil dissolved in olive oil daily for 2 weeks. Group 5 was treated orally with 0.6 ml olive oil daily for 2 weeks. Result: Histopathological and immunohistochemical examinations were performed on the stomach samples. Ethanol caused severe erosive ulcerative lesions in the gastric mucosa and inflammatory cell infiltrations in the propria mucosa. In immunohistochemical examination, marked increases in interleukin-10 (IL-10), interleukin-1ß (IL-ß) and platelet endothelial cell adhesion molecule 1 (PECAM-1) expressions were observed in this group. Omeprazole treatment significantly reduced these pathological findings. Sweetgum oil provided significant improvement in histopathological and immunohistochemical findings, but the protection was not as effective as omeprazole. Moderate healing effects were also observed with olive oil. Sweetgum oil has a curative effect on chronic gastritis, although it is not as effective as omeprazole. Moreover, olive oil has a curative effect on gastritis. [ABSTRACT FROM AUTHOR]

Nitrofurantoin (NFR) is an antibiotic commonly used in the management of uncomplicated urinary tract infections. The study examined histoarchitectural and biochemical alterations in the liver and kidney of Wistar rats following exposure to nitrofurantoin. Fifteen (15) adult Wistar rats comprising five (5) animals per group were randomly assigned into three groups. Group A was the control group while Groups B and C received 30mg kg-1 and 60mg kg-1 body weight of NFR respectively for thirty (30) days. Data generated from liver and renal functional markers was analyzed on graph pad prism using descriptive statistics and outcomes implicated as standard error of the mean and mean. Mean value differences were evaluated using analysis of variance (ANOVA) considering p<0.05 as statistically significant value. Upshot display periportal hepatitis in the group given 30mg kg-1 of nitrofurantoin, the hepatocytes appeared polygonal and there was vascular congestion with inflammatory cell infiltration in rats given 60mg kg-1 NFR. These features were consistent with inflammatory responses. However, liver function tests showed a significant increase in Alanine transaminase (ALT), Aspartate aminotransferase (AST), and Alkaline phosphatase (ALP) levels across treated groups when rationalized to control group (p<0.05). Also observed is a statistically significant increase in mean serum level of total protein, direct and indirect Bilirubin across treatment groups compared to control. More so, there were features consistent with normal renal histoarchitecture with tubules comprising of multiple segments and corpuscle made up of the Glomerulus surrounded by the podocytes. Conversely, renal function parameters showed a decrease in the urea level across treatment groups. Nitrofurantoin displays no histoarchitectural outcome of the kidney but elucidated negative outcome on the liver histology, therefore caution should be considered when administered as a therapeutic agent. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation, inflammation, and aberrant differentiation. Imiquimod-induced psoriasis in rodent models has been widely used to study the pathogenesis of the disease and evaluate potential therapeutic interventions. In this study, we investigated the efficacy of two commonly used treatments, Clobetasol and Tacrolimus, in ameliorating psoriatic symptoms in an Imiquimod-induced psoriasis Wistar rat model. Interestingly, rat models are poorly evaluated in the literature despite rats displaying several advantages in evaluating pharmacological substances. Psoriasis-like skin lesions were induced by topical application of Imiquimod cream on shaved dorsal skin for seven consecutive days. Following induction, rats in the treatment groups received either a Clobetasol or Tacrolimus ointment once daily for one week, while the control group did not receive any application. Disease severity was assessed using clinical scoring, histological examination, and measurement of proinflammatory cytokine levels. Both Clobetasol and Tacrolimus treatments significantly reduced psoriatic lesion severity compared to the control group. Clinical scoring revealed a decrease in erythema, scaling, transepidermal water loss, and thickness of skin lesions in both treatment groups with a more marked effect with Clobetasol. Histological analysis demonstrated reduced epidermal hyperplasia in treated animals compared to controls. Furthermore, Clobetasol led to a significant reduction in the expression levels of the interleukin-17 (IL-17a and IL-17f) proinflammatory cytokines in lesioned skin. Overall, our findings demonstrated the therapeutic efficacy of both Clobetasol and, in a modest manner, Tacrolimus in attenuating Imiquimod-induced psoriasis-like symptoms in a rat model. These results support the clinical use of these agents in the management of psoriasis and mitigating psoriatic inflammation. They also provide insights into the use of rats as a relevant species for the Imiquimod-induced psoriasis model. [ABSTRACT FROM AUTHOR]

Simple Summary: How to effectively alleviate oxidative stress in pregnant sows and weaning piglets is one of the key issues in the pig industry. Maternal feeding is a key determinant of the composition and activity of the intestinal microbiota in both the mother and the offspring, while the effect of the maternal intake of microbial-derived antioxidants (MA) thereof remains to be elucidated. In the current study, we used Sprague Dawley rats as a model to investigate the impact of maternal MA additive on the microbiota of breastmilk, the maternal ileum, and the intestinal microbiota of the offspring on the day of birth and ten days afterwards, via analysis of 16S rRNA gene sequences. We found that the impact of MA was more obvious on the microbiota of mature milk than on that of colostrum. In addition, MA additive did not significantly affect maternal ileal microbiota, but affected offsprings' colonic microbiota significantly ten days after birth. Collectively, the current study underlines colonic microbiota as a key target affected by maternal MA additive in the offspring with the potential to relieve oxidative stress by enriching beneficial bacteria, as well as aiding in the development of maternal feed for improved health outcomes in both mothers and their offspring. This study can provide a theoretical basis for the development of antioxidant feed and the improvement of animal welfare in the pig industry and elsewhere. In this study, sixteen Sprague Dawley (SD) female rats and eight SD male rats were co-housed to mate. Pregnant SD female rats were fed with a control diet or an MA diet. Breast milk, maternal ileum, and intestinal samples of the offspring were collected at the day of birth and ten days afterwards. The results showed that the impact of MA was more obvious on the microbiota of mature milk (p = 0.066) than on that of colostrum. In addition, MA additive did not significantly affect maternal ileal microbiota, but affected offsprings' colonic microbiota significantly ten days after birth (p = 0.035). From the day of giving birth to ten days afterwards, in addition to the increase in microbial richness and diversity, at genus level, the dominant bacteria of breastmilk changed from Pseudomonas veronii to Bacillus and Lactococcus. Different from breastmilk microbiota, ten days after giving birth, the maternal ileal microbiota and the offsprings' intestinal microbiota were dominated by Lactobacillus. Instead of ileal microbiota, offsprings' colonic microbiota is a key action site of maternal MA additive. Therefore, the current findings have significant implications for the development of maternal feed aimed at modulating the intestinal microbiota of offspring, ultimately leading to improved health outcomes for both mothers and their offspring. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Laboratory Animal Science & Practices / Laboratuvar Hayvanlari Bilimi ve Uygulamalari Dergisi is the property of Ataturk University Coordinatorship of Scientific Journals and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: Vitamin B complexes are frequently used in clinical practice for peripheral nerve trauma. However, there is a lack of scientific data on their effectiveness. This study aims to investigate the impact of the vitamin B complex on nerve recovery in a rat model of peripheral nerve paralysis. Materials and Methods: Sixty male Wistar Albino rats were divided into six groups. Models of nerve injury, including blunt trauma, nerve incision, and autograft, were performed on all rats approximately 1 cm distal to the sciatic notch. B-complex vitamins were injected intraperitoneally at 0.2 mL/day to the treatment groups. The control groups were given 0.2 mL/day saline. After 1 month, the study was terminated, electromyography (EMG) was performed to measure the conduction velocity, and nerve tissue was taken from the repair line. The sciatic function indexes (SFIs) were calculated and analyzed. The histopathological samples were stained with hematoxylin and eosin and Toluidine blue and examined with a light microscope. Pathologically, myelination, fibrosis, edema, and mast cell densities in the nervous tissue were evaluated. Results: The vitamin B treatment groups demonstrated significant improvements in SFI compared to the control groups, indicating functional improvement in nerve damage (p < 0.05). In the nerve graft group, the vitamin B group showed a shorter latency, higher velocity, and larger peak-to-peak compared to the controls (p < 0.05). In the nerve transection group, the vitamin B group had better latency, velocity, and peak-to-peak values than the controls (p < 0.05). In the crush injury group, the vitamin B group exhibited an improved latency, velocity, and peak-to-peak compared to the controls (p < 0.05). Better myelination, less fibrosis, edema, and mast cells were also in the vitamin B group (p < 0.05). Conclusions: Vitamin B treatment significantly improves nerve healing and function in peripheral nerve injuries. It enhances nerve conduction, reduces fibrosis, and promotes myelination, indicating its therapeutic potential in nerve regeneration. [ABSTRACT FROM AUTHOR]

BACKGROUND: A network-based pharmacological approach has identified multifunctional effects of the main bioactive compounds in the Trichosanthis Fructus-Allii Macrostemonis Bulbus on coronary heart disease; however, the mechanism of its therapeutic effect on coronary heart disease has not been fully elucidated. OBJECTIVE: To investigate the role and mechanism of Trichosanthis Fructus-Allii Macrostemonis Bulbus in improving coronary heart disease by regulating the composition of gut microbiota. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups: blank control group (n=10), model group (n=10), positive drug group (n=10), and medicine pair group (n=10). A rat model of coronary heart disease was established by continuous gastric perfusion of fat emulsion and injection of pituitrin. After modeling, rats in the model group were gavaged with distilled water (10 mL/kg) for control, rats in the positive drug group were gavaged with simvastatin 4 mg/kg per day, and rats in the medicine pair group were gavaged with Trichosanthis Fructus-Allii Macrostemonis Bulbus pairs 7.56 g/kg per day. All interventions lasted for 14 days. Electrocardiograms and myocardial pathology were observed, and blood lipid levels were measured. The structure of gut microbiota was analyzed using 16S rDNA sequencing technology. RESULTS AND CONCLUSION: Electrocardiogram results showed ST segment elevation in the model group. There were no significant abnormalities in the electrocardiograms of the positive drug group and medicine pair group. Compared with the blank control group, the levels of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol were significantly higher in the model group (P < 0.05). Compared with the model group, the levels of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol were significantly lower in the positive drug group and medicine pair group (P < 0.05). Compared with the blank control group, focal myocardial cell necrosis was observed in the model group, while partial myocardial cell disarray was observed in the positive drug group and medicine pair group. Compared with the blank control group, the Ace, Shannon, and Chao indices were increased (P < 0.05) and the Simpson index was decreased (P < 0.05) in the model group, positive drug group and medicine pair group. Compared with the model group, the Ace and Chao indices were decreased (P < 0.05), while the Shannon index showed no significant difference (P > 0.05) and the Simpson index was also decreased (P < 0.05) in the positive drug group and medicine pair group. Compared with the blank control group, the relative abundances of Desulfovibrionia, Muribaculaceae_norank, etc. were increased in the model group, while those of Clostridia, [Eubacterium]_coprostanoligenes_group_norank, etc. were decreased. Compared with the model group, the relative abundances of WPS-2_norank, Muribaculaceae_norank, etc. were increased in the medicine pair group, while those of Clostridia, [Eubacterium]_coprostanoligenes_group_norank, etc. were decreased; the relative abundances of Desulfobacterota, [Eubacterium]_coprostanoligenes_group_ norank, etc. were increased in the positive drug group, while those of Firmicutes, Muribaculaceae_norank, etc. were decreased. Compared with the positive drug group, the relative abundances of Desulfobacterota, Bacteroides, etc. were increased in the medicine pair group, while those of Firmicutes, [Eubacterium]_ coprostanoligenes_group_norank, etc. were decreased. The LEfSe results showed that the medicine pair group had the highest microbial enrichment, followed by the blank control group and positive drug group, with the model group having the lowest microbial enrichment. To conclude, Trichosanthis Fructus-Allii Macrostemonis Bulbus pairs can improve the development of coronary heart disease by regulating gut microbiota composition, providing new insights for further research and development of Trichosanthis Fructus-Allii Macrostemonis Bulbus pairs. [ABSTRACT FROM AUTHOR]

Background and aim: Zhumeria majdae, a unique native plant of southern Iran, has been traditionally used to treat various health issues. Preclinical studies suggest its therapeutic potential for immunological and inflammatory disorders. This study investigates the effect of Z. majdae essential oil (ZMEO) on TNBS-induced colitis in rats, focusing on the NF-κB/p38 MAPK/Nrf-2 pathway. Experimental procedure: Forty-eight male Wistar rats were used, with all groups except the sham group receiving a single intra-rectal dose of TNBS. Three different doses of ZMEO and also 1 mg/kg dexamethasone were administered orally for 2 weeks. Colon tissue was analyzed for ulcer index, histological changes, inflammatory cytokines, apoptotic factors, and levels of NF-κB, p38 MAPK, and Nrf-2. Key results: GC-mass analysis identified 25 compounds with linalool (52.01%) and camphor (31.01%) as the major compounds in ZMEO. ZMEO ameliorated colon injuries, reduced ulcer index, and prevented the elevation of pro-inflammatory cytokines and pro-apoptotic proteins. It also increased the levels of IL-10 and Bcl-2 proteins. Furthermore, ZMEO decreased the expression of p-NF-κB and p38 MAPK while increasing the expression of pNrf-2. Conclusions: ZMEO mitigates colon damage associated with IBD by suppressing inflammatory cytokines and pro-apoptotic proteins possibly through modulating the NF-κB/p38 MAPK/Nrf-2 signaling pathway. [ABSTRACT FROM AUTHOR]

Objective(s): Activating apoptosis and oxidative stress contributes to the pathogenesis of diabetes. Evening primrose oil (EPO) has been shown to regulate lipid profiles and hyperglycemia under metabolic conditions. This study aimed to examine the effect of EPO on miR-21 expression, oxidative stress, apoptosis, and histological changes in the pancreas of male rats with experimental diabetes induced by streptozotocin (STZ). Materials and Methods: Thirty-two Wistar rats were divided into four distinct groups: control, diabetic, diabetic + EPO, and EPO. EPO was administered orally at a dose of 500 mg/kg, and STZ was administered intraperitoneally at a dose of 35 mg/kg for 28 days. In the end, the effects of treatments were assessed by measuring expressions of miR-21 in the pancreas with real-time PCR, pancreatic histological and immunohistochemical changes examinations, and oxidative stress assessment. Results: In the diabetic group, miR-21 expression and the levels of caspase-3 and malondialdehyde (MDA) were increased compared to the control group, while insulin expression and superoxide dismutase activity (SOD) levels were decreased significantly. Treatment with EPO resulted in a reduction of miR-21 and caspase-3 expression, as well as MDA levels, and an increase in insulin expression and SOD levels compared to the diabetic group. Additionally, supplementation with EPO demonstrated the ability to restore pancreatic tissue features, serum insulin levels, and blood glucose fluctuations. Conclusion: Collectively, the protective impacts of EPO in diabetic rats may be linked to the inhibition of miR-21/caspase-3/oxidative stress pathway, leading to the restoration of pancreatic β-cell function and structure. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a leading factor in end-stage renal disease. The complexity of its pathogenesis, combined with the limited treatment efficacy, necessitates deeper insights into potential causes. Studies suggest that ferroptosis-driven renal tubular damage contributes to DKD's progression, making its counteraction a potential therapeutic strategy. Quercetin, a flavonoid found in numerous fruits and vegetables, has demonstrated DKD mitigation in mouse models, though its protective mechanism remains ambiguous. In this study, we delved into quercetin's potential anti-ferroptotic properties, employing a DKD rat model and high glucose (HG)-treated renal tubular epithelial cell models. Our findings revealed that HG prompted unusual ferroptosis activation in renal tubular epithelial cells. However, quercetin counteracted this by inhibiting ferroptosis and activating NFE2-related factor 2 (Nrf2) expression in both DKD rats and HG-treated HK-2 cells, indicating its renal protective role. Further experiments, both in vivo and in vitro, validated that quercetin stimulates Nrf2. Thus, our research underscores quercetin's potential in DKD treatment by modulating the ferroptosis process via activating Nrf2 in a distinct DKD rat model, offering a fresh perspective on quercetin's protective mechanisms. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate whether cumulative dose‐dependent isotretinoin (Roaccutane®) could affect orthodontic tooth movement (OTM) and root resorption. Materials and Methods: Ninety male Wistar Albino rats were divided into 4 groups. While, the control (SALINE), solvent (SOYBEAN) and orthodontic drug (ISOTM) groups underwent orthodontic force, the non‐orthodontic drug group (ISO) did not. The rats were administrated saline, soybean oil (SBO) and isotretinoin diluted in SBO (ISOTM, ISO) for 30 days, respectively. Six rats were euthanized in each orthodontic group. Fifty grams of orthodontic force was applied to the remaining rats' first molars using the incisors as anchorage. Six more rats in each group were euthanized on the 7th, 14th and 21st days of the force application. In the ISO group, six rats were euthanized on the 37th, 44th and 51st days of administration. Six rats that were euthanized for ISOTM on the 30th day were also used for ISO to reduce the number of rats used. Micro‐computed tomography (micro‐CT) and histological analysis were performed. Results: Independent of orthodontic force, isotretinoin caused root resorption in the apical region. However, there was no statistically significant influence of isotretinoin on OTM and orthodontically induced root resorption (OIRR). Conclusions: Despite the lack of strong evidence supporting the orthodontically induced resorptive effect of isotretinoin, this study provided findings regarding the resorptive effects of isotretinoin on non‐orthodontic root resorption. Therefore, the present results underscore the importance of close monitoring during orthodontic treatment to mitigate potential root resorption in patients who use isotretinoin because of acne complaints. [ABSTRACT FROM AUTHOR]

Orthodontic patients often suffer from mucosal discomfort due to the friction stimulation of orthodontic components on the oral mucosa, and semiconductor laser can treat the oral mucosal discomfort caused by orthodontic treatment, such as redness, swelling, ulcers, etc. This study innovatively created a persistent traumatic environment in the mouth of rats to simulate the intraoral conditions of orthodontic patients, with the aim of using animal models to broaden the understanding of semiconductor laser repair mechanisms of orthodontic traumatic ulcers. 32 male Wistar rats were randomly divided into 6 groups: 1) blank control group; 2) control group; 3) chlorhexidine group; 4) laser group 1; 5) laser group 2; 6) laser group 3. The research contents included ulcer healing degree score, enzyme-linked immunosorbent assay, histological observation of stained sections of ulcer tissue, and analysis of microbial attachment on ulcer surface. The results showed that the continuous traumatic environment significantly prolonged the healing time of ulcer (P<0.05). During the ulcer duration, the proinflammatory factor level was lower, the anti-inflammatory factor level was higher and the healing score was better in the laser group (P<0.05). The antibacterial effect of semiconductor laser is less than 0.12% chlorhexidine solution; Hematoxylin-eosin tissue sections showed lower inflammatory cell infiltration and better epithelial healing in the laser group. This study shows that continuous traumatic environment can delay ulcer healing, and semiconductor laser with appropriate irradiation time is superior to traditional 0.12% chlorhexidine solution in reducing inflammation, relieving pain and promoting ulcer tissue healing. Compared with previous studies, the animal model in this study has made some progress and is closer to the real oral conditions of orthodontic patients. The results further demonstrated the potential of semiconductor laser in the treatment of oral traumatic ulcers during orthodontics. [ABSTRACT FROM AUTHOR]

Background: Carbon monoxide (CO), influences ovarian function, pregnancy, and placental health. Heme oxygenase (HO)-1 and its products, including CO, exhibit protective and anti-inflammatory properties. Objective: This study investigates the protective effects of CO released by the carbon dioxide-releasing molecule (CORM)-2 against oxidative stress, functional and structural changes of the ovaries, and HO-1 expressions in female rats suffering from polycystic ovary syndrome (PCOS). Materials and Methods: In this experimental study, 24 Rattus norvegicus var. Albinus female rats (180-200 gr, 8 wk) were randomly divided into 4 groups (n = 6/each): control, CORM-2 (10 mg/kg), PCOS (induced by 4 mg/kg, intramuscular injection and a single dose of estradiol valerate), PCOS + CORM-2. Ovary histological changes were evaluated by crystal violet staining. Malondialdehyde (MDA) level and superoxide dismutase (SOD) activity of ovarian tissue were assessed using enzyme-linked immunosorbent assay. HO-1 expression was evaluated using Western blot. Results: Corpus luteal formation significantly decreased in the PCOS group and was significantly restored with CORM-2 administration compared to the control group (p < 0.05). The expression of ovarian HO-1 protein was reduced in the PCOS group compared to controls (p < 0.01), and administration of CORM in PCOS rats significantly increased its expression (p < 0.0001). In addition, CORM administration markedly reduced ovarian MDA levels and restored SOD activity (p < 0.0001). Conclusion: CORM-2 administration to PCOS rats created protective effects by reducing oxidative stress (reducing MDA level and restoring SOD activity) and increasing ovarian HO-1 protein. [ABSTRACT FROM AUTHOR]

Background: Teucrium polium a member of Lamiaceae family is a widely used plant in Algerian traditional medicine; however, there are few reports on its use as a healing agent. The aim of this study is to investigate the wound healing property of aerial part of this plant on excisional wounds. Methods: Twenty adult male Wistar rats with an average weight of 180 g were used in this study. Post wound development, 10 rats received daily treatment with the plant ointment and the remaining rats served as control. Measurement of wound areas and calculation of closure percentages were made in order to evaluate wound healing macroscopically and a sample of the scar tissue formed was submitted at day 24 post treatment for a histological study. Result: Better and faster healing was observed in the Teucrium polium group compared to control. This improvement in wound healing was confirmed by the histological study which revealed that the effect of the plant lies in its stimulation of proliferative phase and its regulation of the inflammatory phase of wound healing. Based on these results, we could deduce that Teucrium polium enhance healing of excisional wounds. [ABSTRACT FROM AUTHOR]

The reactivity of an electroencephalogram (EEG) to external stimuli is impaired in comatose patients showing burst-suppression (BS) patterns following hypoxic–ischemic brain injury (HIBI). We explored the reactivity of BS induced by isoflurane in rat models of HIBI and controls using intermittent photic stimulation (IPS) delivered to one eye. The relative time spent in suppression referred to as the suppression ratio (SR) was measured on the contralateral fronto-occipital cortical EEG channel. The BS reactivity (BSR) was defined as the decrease in the SR during IPS from the baseline before stimulation (SRPRE). We found that BSR increased with SRPRE. To standardize by anesthetic depth, we derived the BSR index (BSRi) as BSR divided by SRPRE. We found that the BSRi was decreased at 3 days after transient global cerebral ischemia in rats, which is a model of brain injury after cardiac arrest. The BSRi was also reduced 2 months after experimental perinatal asphyxia in rats, a model of birth asphyxia, which is a frequent neonatal complication in humans. Furthermore, Oxytocin attenuated BSRi impairment, consistent with a neuroprotective effect in this model. Our data suggest that the BSRi is a promising translational marker in HIBI which should be considered in future neuroprotection studies. [ABSTRACT FROM AUTHOR]

Momordica charantia (MC) is a traditional plant widely used since ancient times for wound healing. This study evaluated its potential effects on tendon healing. Adult male Wistar albino rats (n = 32, 8 rats in each group) were anesthetized, and their Achilles tendons were prepared for surgical procedures. Group 1 (Cont = control group) was not subjected to any surgery and was used as a control group for baseline values. Group 2 (PR = primary repair group) underwent primary repair (PR) with a monofilament suture after a full-thickness incision of the Achilles tendon. A full-thickness incision was also made to the Achilles tendon of group 3 (CT = collagen tube-administered group), followed by PR and collagen tube insertion. In group 4 (MC = M. charantia-administered group), 1 mL of MC extract was applied locally on the collagen tube in addition to the surgical procedure applied to group 3. The Achilles tendons were excised on the postoperative 40th day and examined stereologically, histologically, and bioinformatically. Data showed that the total volume of the collagen fibers was higher in MC and CT groups than in the PR group. The total volume of the tendon was decreased in MC and CT groups than in the Cont group. The ratios between the volumes of the collagen fibers and total tendon in the MC and CT groups were significantly different from PR, but not different from the Cont group. Additionally, MC improved tenoblastic activity, collagen production, and neovascularization. Bioinformatic interactions showed that the proteases of MC could trigger the signals playing a role on vasculogenesis, reducing inflammation, and contributing to tenoblast activation and collagen remodeling. MC extract ameliorates the healing of injured tendon and can provide satisfactory tendon repair. Further works are recommended to explore the healing capacity of MC. [ABSTRACT FROM AUTHOR]

Objective(s): Stress elicits physiological and neuroendocrine responses mediated by the hypothalamic-pituitary-adrenal (HPA) axis and lateral hypothalamus (LH). However, prolonged stress can dysregulate neuropeptide systems like orexin. This study investigated the effects of temporary and prolonged stress on HPA activity and orexin processing in the rat LH. Materials and Methods: Male Wistar rats were exposed to various stress repetitions. The stress paradigm is defined as short (acute; 1 day and mild; 3 days) and long (sub-chronic; 10 days and chronic; 21 days)-term 6 hr daily restraint stress. Plasma corticosterone (CORT) served as an index of HPA function. Expression of prepro-orexin and its processing enzymes prohormone convertases (PC) 1 and 2 was measured in LH tissues using semiquantitative RT-PCR. Results: The plasma level of CORT was elevated following mild, sub-chronic, and chronic, but not acute stress versus unstressed controls. The expression of prepro-orexin was heightened following all stress exposures. However, PC1 increased and PC2 decreased only after prolonged stress. The PC1/PC2 ratio was also selectively augmented with sub-chronic and chronic stress, implying impaired orexin maturation. Conclusion: Together, these data demonstrate that the HPA axis and lateral hypothalamic orexin system respond to stress based on stress repetition. Changes in orexin processing enzyme mRNA, exclusively after chronic stress, imply potential effects on peptide maturation, requiring confirmation of the orexin production at the protein level. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most widespread type of primary liver cancer. Diethylnitrosamine (DEN), a hepatotoxic hepatocarcinogenic compound, is used to induce HCC in animal models. The non‐selective β‐blocker propranolol demonstrated antiproliferative activity in many cancer types. Objective: This investigation aimed to evaluate the anticancer effect of propranolol against DEN‐induced HCC in rats. Methods: Thirty adult male rats were divided into the following groups: Group I (C, control), Group II (HCC); received DEN, 70 mg/kg body weight (b.wt.) once a week for 10 weeks, to induce HCC, and Group III (HCC/Prop); received DEN for 10 weeks for HCC induction, then received 20 mg/kg b.wt. propranolol, intraperitoneally for four successive weeks. Results: HCC was developed in rats' livers and confirmed via significant liver architecture changes, significantly elevated activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), α‐fetoprotein (AFP), total‐ and direct‐bilirubin (Bil), and a decline in albumin (ALB) level in serum. HCC group demonstrated elevated levels of malondialdehyde (MDA), nitric oxide (NO), HIF‐1α, IL‐8, NF‐κB, PGE2, TGF‐β1, VEGF, and CD8, but significant decline of GSH, and IL‐10 level, with suppression of the antioxidant enzymes' activities. In addition, the gene expression of the hepatic inducible nitric oxide synthase (iNOS), and LAG‐3 were up‐regulated. Moreover, the protein expression of p‐PKC was up‐regulated, while that of PD‐1 and PD‐L1 were down‐regulated in the liver tissues of the HCC group. However, propranolol ameliorated the investigated parameters in the HCC/Prop group. Conclusion: Propranolol exhibited an anticancer effect and thus can be considered as a promising treatment for HCC. Blocking of PD‐1/PD‐L1 and LAG‐3 signals participated in the anti‐tumor effect of propranolol on HCC. [ABSTRACT FROM AUTHOR]

The article presents a study which observed whether probiotic supplements (PBS), through the gut-brain axis in drug addiction, can decrease morphine (Mor) tendency in rats by affecting oxidative stress (OS) markers, using a conditioned place preference (CPP) paradigm. Topics include definition of the term "microbiome," preparation and administration of the probiotics, and influence of PBS on mood and behavior via antioxidative/oxidative signaling.

Drug iatrogenicity is a constantly evolving phenomenon, affecting several therapeutic classes. The aim of the present study was to investigate the effects of prolonged administration of oxycodone hydrochloride, a central analgesic, on reproductive functions in male rats. Materials and methods: three groups of 5 rats each were created; distilled water 0.5 ml/100g, oxycodone hydrochloride 5 and 10 mg/kg. The different products were administered orally daily for 30 days. The variables studied were: animal behaviour, prostate, testicular and epididymal weights, spermogram parameters and hormonal biomarkers (FSH, LH and testosterone levels). Results: behaviorally and morphologically, the results obtained show that oxycodone hydrochloride at doses of 5 and 10 mg/kg causes stiffness of the animals' tails, priaprism and atrophy of the prostate, testicles and epididymis, of which intensity was dose-dependent. On spermogram parameters, oxycodone hydrochloride caused a significant decrease in sperm motility (p<0.001) and in the number of normal spermatozoa (p<0.05). Administration of oxycodone hydrochloride to rats significantly decreased testosterone levels (p<0.05) and an increase in LH levels. Conclusion: Oxycodone hydrochloride, administered to animals at doses of 5 and 10 mg/kg, causes morphological disturbances of the gonads and related structures, spermogram parameters and gonadal hormones. [ABSTRACT FROM AUTHOR]

Oxidative stress and inflammation are crucial factors contributing to the occurrence and development of vascular dementia (VD). In a previous study, we demonstrated that brozopine (BZP) is an anti-ischemic drug. In this study, a model of VD in rats with modified permanent bilateral common carotid artery occlusion (2-VO) was established in vivo, a model of cellular excitotoxicity/oxidative stress was established via L-glutamate-induced PC12 cell injury, a model of neuroinflammation was established in LPS-induced BV2 cells in vitro, and the ameliorative effect of BZP on cognitive impairment was assessed. BZP treatment improved memory deficit in VD rats through inhibiting Ca2+overload and the levels of oxidative stress, ferroptosis, and inflammatory markers (IL-1β, IL-6, and COX-2) in different brain regions. Additionally, we found that the levels of inflammatory markers in the plasma were also reduced in the VD rats. BZP was further found to have antioxidative stress, antiferroptosis (ferroptosis markers: GPX4, P53, and ACSL4), and antineuroinflammatory effects in PC12 and BV2 cells. Its mechanisms of action were found to be related to the activation of the Nrf2/TLR4/NF-κB pathway; the protective effect of BZP was partially inhibited after using Nrf2-specific inhibitors. Thus, BZP has therapeutic properties for the potential mitigation of cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Social behaviour plays a key role in mental health and wellbeing, and developing greater understanding of mechanisms underlying social interaction—particularly social motivation—holds substantial transdiagnostic impact. Common rodent behavioural assays used to assess social behaviour are limited in their assessment of social motivation, whereas the social operant conditioning model can provide unique and valuable insights into social motivation. Further characterisation of common experimental parameters that may influence social motivation within the social operant model, as well as complementary methodological and analytical approaches, are warranted. Methods: This study investigated the effects of biological sex, housing condition, and time-of-day, on social motivation using the social operant model. This involved training rats to lever press (FR1) for 60-s access to a social reward (same-sex conspecific stimulus). Subjects were male and female Wistar rats, housed under individual or paired conditions, and sessions were conducted either in the mid-late light phase (ZT6-10) or early-mid dark phase (ZT13-17). A behavioural economics approach was implemented to measure social demand and the influence of stimulus partner sex (same- vs. opposite-sex stimulus) on social operant responding. Additionally, video tracking analyses were conducted to assess the degree of convergence between social appetitive and consummatory behaviours. Results: Biological sex, housing conditions, the interaction between sex and housing, and stimulus partner sex potently influenced social motivation, whereas time-of-day did not. Behavioural economics demonstrated that sex, housing, and their interaction influence both the hedonic set-point and elasticity of social demand. Video analysis of social interaction during social operant sessions revealed that social appetitive and consummatory behaviours are not necessarily convergent, and indicate potential social satiety. Lastly, oestrus phase of female experimental and stimulus rats did not impact social motivation within the model. Conclusions: Social isolation-dependent sex differences exist in social motivation for rats, as assessed by social operant conditioning. The social operant model represents an optimal preclinical assay that comprehensively evaluates social motivation and offers a platform for future investigations of neurobiological mechanisms underlying sex differences in social motivation. These findings highlight the importance of continued consideration and inclusion of sex as a biological variable in future social operant conditioning studies. Plain English summary: Humans are social creatures—our everyday interactions with others and the support this provides play a key role in our wellbeing. For those experiencing mental health conditions, people's motivation to engage with others can wane, which can lead them to withdraw from those who support them. Therefore, to develop better treatment strategies for these conditions, we need to gain a deeper understanding of social motivation. Studying social behaviour in animals can facilitate this investigation of social motivation as it allows for a causal understanding of underlying neurobiology that is not possible in human experiments. An optimal way to study social motivation in animals is using the social operant conditioning model, where rats learn to press a lever that opens a door and allows them to interact with another rat for a short time. This study characterised the social operant model by testing whether sex, housing conditions, time-of-day, and the sex of the stimulus partner influence rats' motivation to seek interaction with another rat. We found that female rats were more socially motivated than males, and that rats living alone were more motivated than those living with another rat; interestingly, this effect of housing affected females more than males. Regardless of sex, rats were more motivated to interact with a rat of the opposite sex. These findings provide insights into sex differences in social motivation in rats and new insights into the social operant model which will help guide future research into social motivation and other mental health conditions. Highlights: Female Wistar rats exhibited greater social motivation than male rats in the social operant conditioning model. Isolated housing produced higher social motivation than paired housing, but this isolation-induced increase was either more marked for, or only present in, female rats. Both female and male rats demonstrate higher motivation for opposite-sex than same-sex stimulus conspecifics. Time-of-day and oestrus phase (of female experimental and stimulus rats) did not appear to impact social motivatio. Both between- and within-session behavioural economics in conjunction with video tracking analyses can be applied to better assess social motivation and interaction during social operant conditioning. [ABSTRACT FROM AUTHOR]

Simple Summary: Light is vital to many aspects of normal physiological functioning and behavior; however, the ideal lighting conditions for laboratory rats is unknown. The aim of this study was to determine rats' preferences for the spectral make-up of light created by red or clear cages at high and low light levels (25 or 200 lux). Rats' preferences were tested three times with a free choice test as they matured. Most rats preferred dim light to bright light, no matter the color. But some rats from clear and bright cages preferred clear light more; however, this did change with experience. Furthermore, the rats' sex, type, and behavior mattered for their choices. This study concludes that darker environments are more likely to improve rat welfare by providing a condition they prefer, but the spectral make-up of the light created by red-tinted cages was not aversive. Light is a key factor influencing the welfare of laboratory rodents, but little is known about their optimal lighting condition. It i common knowledge that rats prefer dim light, so bright light is mitigated with red-tinted shelters or cages, which alter both the color and intensity of light. Because both aspects are altered, the contribution of each feature to rodent preference is unknown. Further, it is unknown if this preference is influenced by previous experience. We hypothesized that rats would prefer lower light intensity and that their preferences would be influenced by their housing environment. Breeder pairs of rats were randomly separated into four treatments groups: red 200 lux, red 25 lux, clear 200 lux, and clear 25 lux. The breeders' offspring were tested three times in an apparatus that offered access to each environment, and their preferences were analyzed. Generally, the rats preferred the lower-lux environments and showed no color preference. However, the rats from the clear, 200 lux cages, preferred clear caging and only showed a preference for 25 lux conditions during the second and third preference tests. These results suggest that the light intensity, more than color, should be considered when designing rodent housing and testing facilities. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of platelet rich plasma (PRP) and streptokinase (SK) on postoperative intra-abdominal adhesion formation in rats. The 4-month-old, healthy, non-pregnant female Wistar-Albino rats were used as animal material. The remaining 24 animals were divided into three groups with 8 rats in each group (PRP, SK and Control). The fibroblast proliferation, mononuclear cell infiltration and giant cells were clearly prominent in control group. A decrease was observed in the ratio of these cells in the PRP and SK groups. The comparison of the expression levels of vWF, CASP3 and IL-6 genes showed that the vWF gene was downregulated in the SK group and the IL-6 gene was downregulated in the PRP and SK groups. They were statistically significantly compared to the control group. It was concluded that the expression level of CASP3 gene decreased in the PRP and SK groups compared to the control group, but this decrease was not statistically significant. The PRP and SK could be applied intraperitoneal to prevent the adhesions after intra-abdominal surgery. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the short-term effects of statins on rat skeletal muscle with the use of electrophysiological methods. A total of 28 adult male Wistar albino rats were given atorvastatin, rosuvastatin, and pravastatin (40 mg/kg each) intragastrically for four weeks. At the end of the study, the gastrocnemius muscle was isolated from the surrounding tissues under deep anaesthesia. It was tied with silk thread in the Achilles tendon area and then connected to an isometric force transducer. The contractile properties of the gastrocnemius muscle were assessed. Serum levels of total cholesterol and creatine kinase (CK) were measured. The muscle tissue samples were stained with hematoxylin eosin and histopathologically evaluated under light microscope. The findings revealed that cholesterol levels were significantly lower in all groups except the control group, whereas CK levels were higher in the statin groups than the control group. All three statins decreased the contractile strength and caused fatigue quickly in the gastrocnemius muscle. Histopathological changes in gastrocnemius muscle were more related to early moderate necrosis in rats that were received statins. This study demonstrates that all three statins decrease the ability of skeletal muscle to generate force and its resistance to fatigue in rats. [ABSTRACT FROM AUTHOR]

In this study, the suppressive effects of vincristine and Turkish mad honey alone and in co-applications were biochemically, hematologically, and histopathologically investigated in a mammary tumor model induced with 7,12-dimethylbenz[a]anthracene (DMBA) in rats. A total of 72 rats, 43-49 days old, were divided into 6 groups of 12 rats each. The control group (CG) consisted of healthy rats. The vehicle group (VG) received only vehicle substance and the cancer control group (CCG) was given only DMBA. DMBA and the honey group (HG) given group. DMBA and the vincristine (VinG) given group, and DMBA, the vincristine-honey group (VHG) received both Turkish mad honey and vincristine. Turkish mad honey and/or vincristine was given in the last 4 weeks of the 13-week trial period. White blood cell and lymphocyte counts differed significantly in the CCG and VG groups. Alanine transaminase and total protein levels were higher in the CCG and VinG groups. Aspartate transaminase was higher in the CCG, HG and VG groups. Caspase-3 and Bax protein levels were in the HG and VHG groups significantly higher than CCG. In caspase-8 protein level VHG significantly higher than other groups. Caspase -9 protein level was in CG and VG groups significantly lower than other groups. Bcl-xL increased more in the CCG group. Anaplasia was reduced in the HG and VinG groups, although apoptosis and other cellular damages increased. It was concluded that mad honey and vincristine could be considered together as effective therapeutic agents in this model of DMBA-induced breast cancer. [ABSTRACT FROM AUTHOR]

Background: Doxorubicin (DOX) is a chemotherapeutic drug applied clinically for the remedy of cancer, but its possibly life-threatening cardiotoxicity effects remain a concern. Aim: After that, this study evaluates the cardioprotective impacts of Lagenaria siceraria (LSS) oil on DOX induced cardiomyopathy in rats. Methods: Wistar male rats (n = 28, weighting 190-210 g) were arbitrarily allocated into four equal groups. Group 1 control group (CTR) received normal saline orally (1 ml/kg); group 2 (DOX) received DOX (10 mg/kg); group 3 (DOLS) received DOX + 3 g of Lagenaria siceraria seeds oil/kg; group 4 (LSSO) received LSSO (3 g/kg) daily for 18 days. The serum samples were collected to determine the creatine kinase-MB (CK-MB) isoenzyme, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and Troponin I activity. At the same time, the catalase, malondialdehyde (MDA), and reduced glutathione (GSH) were assessed in heart tissues. Additionally, histopathological investigations for the heart tissue were performed. Results: Results revealed no significant change in CK-MB levels between the DOLS group compared to the CTR group (p > 0.05). DOX group confirmed a substantial increase in AST, LDH, and Troponin1 serum levels compared to DOLS and LLSO groups (p < 0.05). The study demonstrated the antioxidant activity of LSS oil against DOX-induced toxicity. The DOX group significantly reduced GSH and catalase levels, with an increase in MDA levels compared to DOLS and LLSO groups. Histopathological analysis showed protective properties of LSS oil against myocardial damage caused by DOX. Conclusion: This study highlights the favorable impacts of LSS oil in mitigating DOX-triggered cardiotoxicity in a rat model. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) affects a large population, resulting in severe cognitive impairments. Although cognitive rehabilitation is an accepted treatment for some deficits, studies in patients are limited in ability to probe physiological and behavioral mechanisms. Therefore, animal models are needed to optimize strategies. Frontal TBI in a rat model results in robust and replicable cognitive deficits, making this an ideal candidate for investigating various behavioral interventions. In this study, we report three distinct frontal TBI experiments assessing behavior well into the chronic post-injury period using male Long-Evans rats. First, we evaluated the impact of frontal injury on local field potentials recorded simultaneously from 12 brain regions during a probabilistic reversal learning (PbR) task. Next, a set of rats were tested on a similar PbR task or an impulsivity task (differential reinforcement of low-rate behavior [DRL]) and half received salient cues associated with reinforcement contingencies to encourage engagement in the target behavior. After intervention on the PbR task, brains were stained for markers of activity. On the DRL task, cue relevance was decoupled from outcomes to determine if beneficial effects persisted on impulsive behavior. TBI decreased the ability to detect reinforced outcomes; this was evident in task performance and reward-feedback signals occurring at beta frequencies in lateral orbitofrontal cortex (OFC) and associated frontostriatal regions. The behavioral intervention improved flexibility and increased OFC activity. Intervention also reduced impulsivity, even after cues were decoupled, which was partially mediated by improvements in timing behavior. The current study established a platform to begin investigating cognitive rehabilitation in rats and identified a strong role for dysfunctional OFC signaling in probabilistic learning after frontal TBI. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in children. We have previously shown that TBI with a concurrent extracranial injury reliably leads to post-injury suppression of the innate and adaptive immune systems. In patients with post-injury immune suppression, if immune function could be preserved, this might represent a therapeutic opportunity. As such, we examined, in an animal injury model, whether systemic administration of granulocyte macrophage colony-stimulating factor (GM-CSF) could reverse post-injury immune suppression and whether treatment was associated with neuroinflammation or functional deficit. Prepubescent male rats were injured using a controlled cortical impact model and then subjected to removal of 25% blood volume (TBI/H). Sham animals underwent surgery without injury induction, and the treatment groups were sham and injured animals treated with either saline vehicle or 50 μg/kg GM-CSF. GM-CSF was administered following injury and then daily until sacrifice at post-injury day (PID) 7. Immune function was measured by assessing tumor necrosis factor-α (TNF-α) levels in whole blood and spleen following ex vivo stimulation with pokeweed mitogen (PWM). Brain samples were assessed by multiplex enzyme-linked immunosorbent assay (ELISA) for cytokine levels and by immunohistochemistry for microglia and astrocyte proliferation. Neuronal cell count was examined using cresyl violet staining. Motor coordination was evaluated using the Rotarod performance test. Treatment with GM-CSF was associated with a significantly increased response to PWM in both whole blood and spleen. GM-CSF in injured animals did not lead to increases in levels of pro-inflammatory cytokines in brain samples but was associated with significant increases in counted astrocytes. Finally, while injured animals treated with saline showed a significant impairment on behavioral testing, injured animals treated with GM-CSF performed similarly to uninjured animals. GM-CSF treatment in animals with combined injury led to increased systemic immune cell response in whole blood and spleen in the acute phase following injury. Improved immune response was not associated with elevated pro-inflammatory cytokine levels in the brain or functional impairment. [ABSTRACT FROM AUTHOR]

Rutin, a phenolic compound, exhibits a diverse range of biological properties, including antioxidant, anti-inflammatory, and antimicrobial effects. In this study, we aimed to investigate the potential of rutin, a naturally occurring plant bioactive molecule, to mitigate the neurotoxic effects induced by aluminum chloride (AlCl 3). Over a period of 6 weeks, rats were intraperitoneally injected with AlCl 3 at a weekly dose of 60 mg/kg, while rutin treatment was administered orally via gavage at a daily dose of 30 mg/kg. AlCl 3 exposure resulted in a significant increase lipid peroxidation (LPO) by 316.24%, nitrate levels by 504.14%, and tumor necrosis factor-alpha (TNF-α) levels by 93.82% in brain mitochondria. Additionally, AlCl 3 exposure led to a reduction in glutathione levels and the activity of antioxidant enzymes, including superoxide dismutase (SOD) by 19.74%, glutathione peroxidase (GPx) by 44.76%, and catalase by 50.50%. There was also a significant decline in the activity of mitochondrial complex enzymes. In contrast, rutin treatment significantly enhanced the activity of antioxidant enzymes while concurrently reducing lipid peroxidation levels in rats. Specifically, rutin administration exerted a modulatory effect on the inflammatory response triggered by aluminum exposure, effectively suppressing the excessive production of nitrate and TNF-α. These findings highlight the potential of rutin as an effective therapeutic strategy in mitigating and combating neuro-inflammation and oxidative stress associated with aluminum-induced toxicity, thereby effectively restoring mitochondrial function. • Ivestigating dietary polyphenols' impact on brain functions, combating oxidative stress and inflammation in neurodegenerative rodent models. • Exploring the influence of dietary polyphenols on neuronal processes, promoting cerebral health by regulating mitochondrial function and inflammation. • Highliting rutin's therapeutic potential in relieving neuro-inflammation and oxidative stress caused by aluminum toxicity, restoring mitochondrial function effectively. [ABSTRACT FROM AUTHOR]

The current study examines the effects of linalool in preventing postoperative abdominal adhesions. Twenty male Wistar rats were randomly divided into four groups. (1) Sham: in this group, the abdomen was approached, and without any manipulations, it was sutured. (2) Control: rats in this group underwent a surgical procedure to induce adhesions. This involved making three incisions on the right abdominal side and removing a 1×1-cm piece of the peritoneum on the left abdominal side. (3) Treatment groups: these groups underwent the same surgical procedure as the control group to induce adhesions. Animals in these groups received linalool orally with doses of 50 and 100 mg/kg, respectively, for a period of 14 days. Moreover, rats in the sham and control groups received normal saline via gavage for 14 days. The evaluation of TNF-α, TGF-β, VEGF, and caspase 3 was performed using western blot and IHC methods. Furthermore, oxidative stress biomarkers such as MDA, TAC, GSH, and NO were assessed in the peritoneal adhesion tissue. The findings revealed that linalool significantly reduced peritoneal adhesions by reducing TNF-α, TGF-β, VEGF, and caspase 3 levels. Moreover, MDA concentration was significantly decreased, while NO, TAC, and GSH levels were notably increased. Overall, linalool was effective in preventing adhesion formation and reduced inflammation, angiogenesis, apoptosis, and oxidative stress. Therefore, linalool as a potent antioxidant is suggested for reducing postoperative adhesions in rats. [ABSTRACT FROM AUTHOR]

Background and objectives: Clinical studies have consistently identified depression-related disorders as the most prevalent neuropsychiatric symptoms in Alzheimer's disease (AD). Quercetin has garnered significant attention as a therapeutic approach for various neuropsychiatric conditions, particularly symptoms of depression in individuals. This study aimed to compare the neuroprotective effects of quercetin on depression-like behaviors and serum levels of anti-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and galectin (Gal)-3, in a rat model of AD. Methods: Fortyeight Wistar rats were categorized into six groups: control, sham, AD, quercetin 10, quercetin 25, and quercetin 100 mg/kg body weight through gavage for 8 weeks. The rat model of AD was induced by intra-cerebroventricular administration of streptozotocin (STZ; 4 mg/rat, bilaterally). Depressive-like behaviors were assessed using the forced swimming test (FST), elevated plus maze (EPM), and open field test (OFT). Additionally, serum Gal-3 and TNF-α concentrations were measured. Results: STZ administration led to increased depression-related behaviors in OFT, EPM, and FST. Significant elevations in serum TNF-α, coupled with a decrease in Gal-3 concentrations in the hippocampus of AD rats, were observed. Remarkably, quercetin treatment reversed hippocampal cytokine concentrations in STZ-treated rats. Quercetin at the doses of 25 and 100 mg/kg significantly increased serum Gal-3 concentrations compared to other groups. Conclusion: The antidepressant effects of quercetin may be linked to its capacity to reduce inflammation and increase Gal-3 levels. [ABSTRACT FROM AUTHOR]

Background: Mutations in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause a severe neurological disorder characterised by early-onset epileptic seizures, autism and intellectual disability (ID). Impaired hippocampal function has been implicated in other models of monogenic forms of autism spectrum disorders and ID and is often linked to epilepsy and behavioural abnormalities. Many individuals with CDKL5 deficiency disorder (CDD) have null mutations and complete loss of CDKL5 protein, therefore in the current study we used a Cdkl5−/y rat model to elucidate the impact of CDKL5 loss on cellular excitability and synaptic function of CA1 pyramidal cells (PCs). We hypothesised abnormal pre and/or post synaptic function and plasticity would be observed in the hippocampus of Cdkl5−/y rats. Methods: To allow cross-species comparisons of phenotypes associated with the loss of CDKL5, we generated a loss of function mutation in exon 8 of the rat Cdkl5 gene and assessed the impact of the loss of CDLK5 using a combination of extracellular and whole-cell electrophysiological recordings, biochemistry, and histology. Results: Our results indicate that CA1 hippocampal long-term potentiation (LTP) is enhanced in slices prepared from juvenile, but not adult, Cdkl5−/y rats. Enhanced LTP does not result from changes in NMDA receptor function or subunit expression as these remain unaltered throughout development. Furthermore, Ca2+ permeable AMPA receptor mediated currents are unchanged in Cdkl5−/y rats. We observe reduced mEPSC frequency accompanied by increased spine density in basal dendrites of CA1 PCs, however we find no evidence supporting an increase in silent synapses when assessed using a minimal stimulation protocol in slices. Additionally, we found no change in paired-pulse ratio, consistent with normal release probability at Schaffer collateral to CA1 PC synapses. Conclusions: Our data indicate a role for CDKL5 in hippocampal synaptic function and raise the possibility that altered intracellular signalling rather than synaptic deficits contribute to the altered plasticity. Limitations: This study has focussed on the electrophysiological and anatomical properties of hippocampal CA1 PCs across early postnatal development. Studies involving other brain regions, older animals and behavioural phenotypes associated with the loss of CDKL5 are needed to understand the pathophysiology of CDD. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to develop a technique for quantitative determination of rat urine metabolites by HPLC–MS/MS, which can be used to search for biomarkers of acute intoxication with organophosphates (OPs). Results: The content of metabolites in the urine of rats exposed to a single dose of paraoxon (POX1x); interval, twice daily administration of paraoxon (POX2x); exposure to 2-(o-cresyl)-4H-1, 3, 2-benzodioxaphosphorin-2-oxide and paraoxon (CBPOX) was investigated. New data were obtained on the content in the urine of intact rats as well as rats in 3 models of OP poisoning: 3-methylhistidine, threonine, creatine, creatinine, lactic acid, acetylcarnitine, inosine, hypoxanthine, adenine, 3-hydroxymethyl-butyrate and 2-hydroxymethyl-butyrate. Conclusions: The proposed assay procedure is a simple and reliable tool for urine metabolomic studies. Within 1–3 days after OP exposure in all three models of acute intoxication, the concentration of metabolites in rat urine, with the exception of adenine, changes similarly and symmetrically, regardless of the method of poisoning modeling, in all three models of acute intoxication. Further studies are needed to determine the specificity and reliability of using urinary metabolite concentration changes as potential biomarkers of acute organophosphate intoxication. [ABSTRACT FROM AUTHOR]

Status epilepticus (SE), the most severe form of epilepsy, leads to brain damage. Uncertainty persists about the mechanisms that lead to the pathophysiology of epilepsy and the death of neurons. Overloading of intracellular iron ions has recently been identified as the cause of a newly recognized form of controlled cell death called ferroptosis. Inhibiting ferroptosis has shown promise as a treatment for epilepsy, according to recent studies. So, the current study aimed to assess the possible antiepileptic impact of CoQ10 either alone or with the standard antiepileptic drug sodium valproate (SVP) and to evaluate the targeted effect of COQ10 on hippocampal oxidative stress and ferroptosis in a SE rat model. Using a lithium-pilocarpine rat model of epilepsy, we evaluated the effect of SVP, CoQ10, or both on seizure severity, histological, and immunohistochemical of the hippocampus. Furthermore, due to the essential role of oxidative stress and lipid peroxidation in inducing ferroptosis, we evaluated malonaldehyde (MDA), reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), and ferritin in tissue homogenate. Our work illustrated that ferroptosis occurs in murine models of lithium-pilocarpine-induced seizures (epileptic group). Nissl staining revealed significant neurodegeneration. A significant increase in the number of astrocytes stained with an astrocyte-specific marker was observed in the hippocampus. Effective seizure relief can be achieved in the seizure model by administering CoQ10 alone compared to SVP. This was accomplished by lowering ferritin levels and increasing GPX4, reducing MDA, and increasing GSH in the hippocampus tissue homogenate. In addition, the benefits of SVP therapy for regulating iron stores, GPX4, and oxidative stress markers were amplified by incorporating CoQ10 as compared to SVP alone. It was concluded that CoQ10 alone has a more beneficial effect than SVP alone in restoring histological structures and has a targeted effect on hippocampal oxidative stress and ferroptosis. In addition, COQ10 could be useful as an adjuvant to SVP in protecting against oxidative damage and ferroptosis-related damage that result from epileptic seizures. [ABSTRACT FROM AUTHOR]

Background: Aspirin or acetylsalicylic acid (ASA) is among the most popular used drugs in the world. Gastric lesions are one of aspirin's often-occurring side effects. Silymarin is a natural compound that exhibits effects against inflammation, oxidation, and apoptosis. Aim of the work: This study was conducted to evaluate ASA-induced gastric mucosal damage and the potential ameliorative role of silymarin. Material and Methods: Thirty adult male albino rats were randomly divided into three equal groups: a control group (subdivided into a negative control group without any medication and a positive control group that received distilled water/day orally by gastric gavage for 2 weeks), ASA-treated group (received 200 mg ASA/kg b.w./day orally for 2 weeks), and ASA+silymarin-treated group (received 200 mg ASA/kg b.w./day in addition to 50 mg silymarin/kg b.w./day, orally for 2 weeks). At the end of the experiment, the rats were anaesthetized and sacrificed. The stomach was removed, opened, and processed for histological and iNOS immunohistochemical evaluation. Area % of collagen fibres and iNOS immune expression and gastric mucosal thickness of all animal groups were measured and compared. Results: The ASA induced gastric mucosal histological changes in the form of erosion, degeneration, vacuolization of cells, and dilatation of blood capillaries. The area % of collagen fibres and iNOS was significantly increased and gastric mucosal thickness was significantly decreased in ASA-treated groups in comparison to the control. These changes were improved in the ASA+silymarin-treated group. Conclusion: ASA induced gastric mucosal injuries and the concomitant administration of silymarin could ameliorate these effects. [ABSTRACT FROM AUTHOR]

Introduction: Chronic use of various compounds can have long-lasting effects on animal behavior, and some of these effects can be influenced by the environment. Many environmental enrichment protocols have the potential to induce behavioral changes. Aim: The aim of the present study was to investigate how environmental enrichment can mitigate the effects of chronic methylphenidate consumption on the behavior of Wistar rats. Methods: The animals were housed for 20 days under either an environmental enrichment protocol (which included tubes of different shapes) or standard housing conditions. After seven days, half of the rats received 13 days of oral administration of methylphenidate (2 mg/kg). After seven days, the rats underwent behavioral tests, including the elevated plus maze (anxiety), open field (locomotion), object-in-place recognition test (spatial memory), and a test for social interaction (social behavior). Results: The results showed that the enriched environmental condition reversed the enhanced time in the open arms of the elevated plus maze induced by methylphenidate (F[1,43] = 4.275, p = 0.045). Methylphenidate also enhanced exploratory rearing in the open field (F[1,43] = 4.663, p = 0.036) and the time spent in the open area of the open field (H[3] = 8.786, p = 0.032). The enriched environment mitigated the inhibition of social interaction with peers induced by methylphenidate (H[3] = 16.755, p < 0.001) as well as the preference for single exploratory behavior (H[3] = 9.041, p = 0.029). Discussion: These findings suggest that environmental enrichment can counteract some of the effects of methylphenidate. These results are relevant for the clinical treatment of the long-lasting secondary effects associated with methylphenidate pharmacological treatment. [ABSTRACT FROM AUTHOR]