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Abstract: In much of the West, including Brazil, drug use has increased since social distancing began in response to the pandemic. Use of smoked and modified drugs, and their impacts on health, may contribute to aggravate the effects of the pandemic. However, studies on the relationship between use of smoked drugs and the new coronavirus are still scarce and have not received enough attention in global health recommendations. This paper aims to briefly review the relationship between use of smoked drugs and acute respiratory syndrome coronavirus 2 [SARS-CoV-2]. Recent studies also suggest that drug consumption increases the risk of contamination by SARS-CoV-2 and leads to worse prognosis, particularly consumption of drugs that affect lung function. Use of smoked drugs, especially tobacco, is strongly associated with lung diseases that are risk factors for contamination by SARS-CoV-2. It is essential to develop strategies based on specific characteristics of drug users and for mental health professionals to be included in strategic teams. It is also necessary to invest in information campaigns regarding risks and prevention of harm caused by smoked drugs as well as to design strategies that facilitate access to psychosocial treatment during the pandemic., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Background: Breast augmentation is the most common aesthetic operation performed in the United States and worldwide; 1,862,506 breast augmentation procedures were performed in 2018, an increase of 27.6 percent compared to 2014 data., Methods: In the present study, the authors performed a systematic review to identify the accuracy of ultrasonography for diagnosing breast prosthesis rupture. Studies in which the ultrasound diagnostic test was compared to a surgical finding as a reference standard were reviewed., Results: As a result, 20 primary studies were included in the analyses, with a total of 1987 patients and 3297 prostheses. The use of ultrasound for diagnosis of breast prosthesis rupture presented the following results: pooled sensitivity, 73.7 percent (95 percent CI, 70.2 to 77.1 percent); pooled specificity, 87.8 percent (95 percent CI, 86.5 to 89.0); area under the receiver operating characteristic curve, 0.7762; diagnostic odds ratio, 11.04 (95 percent CI, 5.79 to 21.08)., Conclusion: This study supports that ultrasound of breast prostheses is an adequate tool in the diagnosis of rupture., (Copyright © 2021 by the American Society of Plastic Surgeons.)

The COVID-19 pandemic is unquestionably impacting on the mental health of the population worldwide. Fear of contamination can both increase levels of stress in healthy individuals and intensify psychiatric symptoms in patients with pre-existing conditions, especially obsessive-compulsive disorder (OCD). During the COVID-19 pandemic, the imminent risk of contamination creates a logical need for self-surveillance and hygiene habits. However, this kind of information can have drastic implications for subjects with OCD, since cognitive distortions and compensatory strategies (cleansing rituals) are no longer irrational or oversized - rather, these ideas become legitimate and socially accepted, generating plausible validation for the intensification of compulsive cleaning rituals. Patients who presented remission of OCD symptoms would be more likely to have a relapse, and subclinical patients may scale up and ultimately be diagnosed with OCD due to the reinforcement of their habits, emotions and thoughts., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Bipolar disorder (BD) is a mood psychiatric disorder described by changes between depressive, hypomanic, or manic episodes. The aimed of the present study was evaluated possible changes in the AA pathway in BD through a systematic review of observational studies. A search in the electronic databases was proceeded, on Cochrane Library, MEDLINE, EMBASE, PsycINFO, Google Scholar and the British Library for studies published until August 2020. A search strategy was developed using the terms: "Bipolar Disorder" and "Phospholipase A2" or "Arachidonic Acids" or "Cyclooxygenase 2" or "Prostaglandins E" as text words and Medical Subject Headings (i.e., MeSH and EMTREE). Seven primary studies were included in the systematic review, with a total of 246 BD patients, 20 depression patients, and 425 heathy controls (HC). The studies showed contradictory results in the AA and PLA2, no primary articles with COX and PGE2 assessments were included in this review. According to the Newcastle-Ottawa quality score scale (NOS), our systematic review presented high quality. The investigation of the inflammatory pathway of AA still needs further investigation and evidence, given the growing number of studies suggesting the efficacy of anti-inflammatory drugs as adjunctive therapy in the pharmacological treatment of BD.

Background: Bipolar Disorder (BD) is a chronic psychiatric disorder characterized by mood disturbances that include depressive, manic, and hypomanic episodes. Despite the severity of the symptoms, there is still a gap in the literature on the precise neurobiology and treatment of BD. The investigations of inflammatory changes in BD has increased in the last decade, evincing the importance of its role in the pathophysiology of the disorder. The present study aimed to investigate the inflammatory role in BD, through the evaluation of biomarkers and their relation to biological rhythms., Methods: It was conducted a case-control study that included 36 BD and 46 healthy controls (HC). The Cyclooxygenase 2 (COX-2) enzyme, Arachidonic Acid (AA), interleukins (IL) IL-4, IL-5, IL-6, IL-10, IL-33, and Tumor Necrosis Factor Alpha (TNF-α) in the serum of individuals. It also was administered the Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) to the BD and healthy control groups., Results: The results indicated that the individuals with BD showed increased COX-2, AA, IL-6, and TNF-α levels in comparison to the HC without psychiatric disorders, as well as significant commitments in all domains evaluated by BRIAN., Limitations: Uncontrolled pharmacotherapy used by the included bipolar participants, which had important effects on participants' inflammatory systems and the lack of cases with bipolar manic episodes., Conclusions: The results of the present study reaffirm that inflammation has an important role in BD, as well as the significant changes in biological rhythms. It is still necessary to better characterize the inflammatory pathway of AA., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Treatment-resistant depression (TRD) denotes the therapeutic failure of at least two evidence-based, dose-based, and time-appropriate treatment regiments for major depressive disorder (MDD). Studies have suggested that alterations in proinflammatory cytokines play an important role in the pathophysiology of TRD, as well as a significant relationship between the number of failed treatment and the levels of tumor necrosis factor-alpha (TNF-α)., Objective: Performed a systematic review and meta-analysis to evaluate the potential effect of the TNF-inhibitor Infliximab adjunct treatment in MDD, through randomized controlled trials (RCT)., Methods: A search in the electronic databases was proceeded, on MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, Web of Science, IBECS, LILACS, PsycINFO, Congress Abstracts, and Grey literature (Google Scholar and the British Library) for studies published until April 2019. A search strategy was developed using the terms: "Mood disorder" OR "Depressive Disorder" OR "Bipolar disorder" AND "Infliximab" OR "tumor necrosis factor antagonist" as text words and Medical Subject Headings (i.e., MeSH and EMTREE). The therapeutic effects of adjunctive treatment with Infliximab were analyzed. The meta-analysis was performed including the results of the Hamilton Scale for Depression (HAM-D)., Results: Four primary studies were included in the systematic review, with a total of 152 patients. The meta-analysis did not show a statistically significant effect of Infliximab as an adjuvant treatment for TRD., Limitations: Articles in this meta-analysis originate from the same country. The main treatments used were different among the included studies., Conclusion: Infliximab was not efficient in reducing depressive symptoms according to the HAM-D, only when the patients already had increased inflammatory genes, including TNF and C-reactive protein (CRP)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Performed a systematic review to evaluated the dopaminergic system in alcohol abuse in a systematic review in humans., Method: A search of the electronic databases was proceeded, on MEDLINE, EMBASE, Cochrane Library, Insight and Gray literature (Google Scholar and the British Library) for studies published until August 2018. A search strategy was developed using the terms: "dopamine" and "ethanol" or ""alcohol"," and "positron-emission tomography" as text words and Medical Subject Headings (i.e., MeSH and EMTREE) and searched., Results: We found 293 studies. After reading titles and abstracts 235 were considered irrelevant, as they did not meet the inclusion criteria. For the reading of the full text, 50 studies were analyzed. Of these 41 were excluded with reasons by study design, patient population, intervention and outcomes. Nine studies were included in our qualitative synthesis. Four studies have resulted in a reduction in availability only at the D2 receptor in different brain regions. Concerning the D3 receptor alone only one study reported this finding and four studies reported a decrease in both receptors., Conclusion: Changes in D2 receptors in several brain regions in human alcoholics were found in a systematic review., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: This systematic review evaluates the accuracy of the mRNA HPV biomarker in cervical smears to identify cervical intraepithelial neoplasia (CIN) 2 or 3 and cervical cancer., Data Source: Eligible studies were identified by performing a search of electronic databases on Medline via Pubmed, Lilacs, Cochrane Library, Embase, and Grey literature for papers published between January 1990 and June 2018., Study Eligibility Criteria: As no randomized studies were identified, this review focuses on observational studies in which the mRNA HPV diagnostic test was compared to a histopathology reference standard. We analyzed studies that included women screened for cervical cancer using mRNA HPV., Study Appraisal and Synthesis Methods: After screening, 61 studies including 29,674 patients met the inclusion criteria and were analyzed. Dichotomization was performed by defining CIN2 or worse (CIN2+) versus CIN1, HPV infection, and normal (CIN 1-). The analysis was discriminated by the following tests: Aptima, PreTect HPV Profeer, NucliSens EasyQ HPV, OncoTect, and Quantivirus., Results: Analyzing by technique, Aptima, with 28 studies, exhibited superior performance, showing for the outcomes CIN2+ and CIN3+ an AUC of 0.88 (0.82-0.95) and 0.91 (0.84-0.99), a pooled sensitivity of 92.8% (95%CI 91.9-93.7) and 95.6% (95%CI 94.5-96.5), and a pooled specificity of 60.5% (95%CI 59.8-61.3) and 61.9% (95%CI 61.1-62.7), respectively., Conclusion: This study supports the current hypothesis that the mRNA HPV assay is an adequate tool for secondary cervical cancer screening.

Objectives: The main objective of this systematic review and meta-analysis is to specify the accuracy of messenger RNA human papillomavirus (HPV) tests among women with previous minor cervical lesion cytology to detect high-grade squamous intraepithelial lesions (CIN2+ and CIN3+) compared with a histopathological reference standard. The secondary objective is to compare messenger RNA HPV test accuracies and the DNA high-risk HPV test among these women., Methods: Eligible studies were identified by searching the electronic databases with medical subject headings., Main Results: Among the 2052 studies identified, 20 primary studies were included. Two tests were mainly identified: Aptima and PreTect HPV-Proofer. Aptima, with 10 studies, had better performance, considering atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion together, with a pooled sensitivity of 90.5% (95% confidence interval [CI], 88.1-92.6) and specificity of 55.1% (95% CI, 53.5-56.8) for CIN2+. For the ASC-US sample, Aptima had a pooled sensitivity of 90.1% (95% CI, 87.1-92.7) and specificity of 59.3% (95% CI, 57.5-61.1)., Conclusions: Messenger RNA HPV tests, mainly Aptima assay, can be recommended to triage women with ASC-US and low-grade squamous intraepithelial lesion because it has higher specificity with a small loss of sensitivity than Hybrid Capture 2 assay; this finding is promising as a means to reduce the overmanagement of minor cytological abnormalities.

Objective: This systematic review evaluates the accuracy of mRNA HPV biomarker for the identification of cervical intra-epithelial neoplasia (CIN) or cervical cancer during a follow-up after conization, taking histopathology as reference standard. Methods: A search of electronic databases was performed, for studies published until June 2018. As results, after screening, five studies including 1148 patients met the inclusion criteria. Dichotomization was performed by CIN2+ versus CIN1-. By analyzing all five studies, a sensitivity of 62.4% (95% CI: 54.8-69.7), specificity of 91.9% (95% CI: 90.0-93.5) and area under the curve of 0.5685 were revealed. Conclusion: mRNA HPV assay presents a high specificity and is an adequate tool for cervical cancer screening in the follow-up after conization.

Background: Bipolar disorder (BD) and substance use disorders share common symptoms, such as behavioral sensitization. Amphetamine-induced behavioral sensitization can serve as an animal model of BD. Neurotrophic factors have an important role in BD pathophysiology. This study evaluated the effects of amphetamine sensitization on behavior and neurotrophic factor levels in the brains of rats., Methods: Wistar rats received daily intraperitoneal (i.p) injections of dextroamphetamine (d-AMPH) 2 mg/kg or saline for 14 days. After seven days of withdrawal, the animals were challenged with d-AMPH (0.5 mg/kg, i.p) and locomotor behavior was assessed. In a second protocol, rats were similarly treated with d-AMPH (2 mg/kg, i.p) for 14 days. After withdrawal, without d-AMPH challenge, depressive- and anxiety-like behaviors were evaluated through forced swimming test and elevated plus maze. Levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT-3), neurotrophin 4/5 (NT-4/5) and glial-derived neurotrophic factor (GDNF) were evaluated in the frontal cortex, hippocampus, and striatum., Results: D-AMPH for 14 days augmented locomotor sensitization to a lower dose of d-AMPH (0.5 mg/kg) after the withdrawal. d-AMPH withdrawal induced depressive- and anxious-like behaviors. BDNF, NGF, and GDNF levels were decreased, while NT-3 and NT-4 levels were increased in brains after d-AMPH sensitization., Limitations: Although d-AMPH induces manic-like behavior, the mechanisms underlying these effects can also be related to phenotypes of drug abuse., Conclusions: Together, vulnerability to mania-like behavior following d-AMPH challenge and extensive neurotrophic alterations, suggest amphetamine-induced behavioral sensitization is a good model of BD pathophysiology., (Copyright © 2018. Published by Elsevier B.V.)

Background: Anal canal carcinoma is relevant because it commonly occurs in high-risk groups, and its incidence has been increasing., Objective: This study evaluated the accuracy of anal cytology in the screening of precursor lesions of anal cancer, compared with histopathologic examination as the reference, in all subjects and in men who have sex with men, HIV-infected men and women, and men who have sex with men and HIV-infected subgroups., Data Sources: The data included studies identified in the MEDLINE, Latin American and Caribbean Health Sciences, Cochrane Library, and Embase electronic databases, as well as in the grey literature. The search terms included anal cancer, anal dysplasia, anal intraepithelial neoplasia, screening, and anal cytology., Study Selection: After excluding studies with no histopathological data and those with duplicate and missing data, 34 primary studies were included., Intervention: Cytology of anal smears was studied., Main Outcome Measures: Sensitivity, specificity, diagnostic OR, and area under the curve were measured., Results: A total of 5093 patients were included. The pooled sensitivity of anal cytology was 85.0% (95% CI, 82.0%-87.0%) and pooled specificity was 43.2% (95% CI, 41.4%-45.1%) for the detection of anal intraepithelial neoplasia grade 2 or worse versus anal intraepithelial neoplasia grade 1 and normal when measuring all subjects. The accuracy of anal cytology was higher in the men who have sex with men and HIV-infected and men who have sex with men only subgroups., Limitations: This study was limited by its specificity., Conclusions: The study results support the hypothesis that cytology is a good test for the screening of anal cancer.

Background: Bipolar Disorder (BD) is a psychiatric disorder characterized by mood disturbances. The pathophysiology of BD is still poorly understood. In the last years, research studies focused on the role of inflammation in BD., Objective: Performed a systematic review and meta-analysis to evaluate the potential effect of the cyclo- oxygenases (Cox)-2 inhibitor Celecoxib adjunct treatment in BD through randomized controlled trials (RCT)., Methods: A search on the electronic databases was proceeded, on MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, Web of Science, IBECS, LILACS, PsycINFO, Congress Abstracts, and Grey literature (Google Scholar and the British Library) for studies published from January 1990 to February 2018. A search strategy was developed using the terms: "Bipolar disorder" or "Bipolar mania" or "Bipolar depression" or "Bipolar mixed" or "Bipolar euthymic" and "Celecoxib" or "Cyclooxygenase-2 inhibitors" or "Cox-2 inhibitors" as text words and Medical Subject Headings (i.e., MeSH and EMTREE) and searched. The therapeutic effects of adjunctive treatment with Celecoxib were analyzed. The meta-analysis was performed including the results of the Young Mania Rating Scale (YMRS) at the end of RCT., Results: Three primary studies were included in the systematic review, with a total of 121 patients. The meta-analysis showed a significant effect on the YMRS scores from patients with BD who used Celecoxib adjuvant treatment in comparison to placebo., Conclusion: The systematic review suggests that adjuvant treatment with Celecoxib improves the response of major treatments in patients with BD when compared with adjuvant placebo treatment. Systematic Review Registration Number: The review protocol was registered at PROSPERO (registration number: CRD42017067635); in June 06 2017., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To evaluate the effects of Hypericum perforatum (hypericum) on cognitive behavior and neurotrophic factor levels in the brain of male and female rats., Methods: Male and female Wistar rats were treated with hypericum or water during 28 days by gavage. The animals were then subjected to the open-field test, novel object recognition and step-down inhibitory avoidance test. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and frontal cortex., Results: Hypericum impaired the acquisition of short- and long-term aversive memory in male rats, evaluated in the inhibitory avoidance test. Female rats had no immediate memory acquisition and decreased short-term memory acquisition in the inhibitory avoidance test. Hypericum also decreased the recognition index of male rats in the object recognition test. Female rats did not recognize the new object in either the short-term or the long-term memory tasks. Hypericum decreased BDNF in the hippocampus of male and female rats. Hypericum also decreased NGF in the hippocampus of female rats., Conclusions: The long-term administration of hypericum appears to cause significant cognitive impairment in rats, possibly through a reduction in the levels of neurotrophic factors. This effect was more expressive in females than in males.

The present study aims to investigate the oxidative stress parameters in isolated mitochondria, as well as looking at mitochondrial complex activity in patients with Bipolar Disorder (BD) during depressive or euthymic episodes. This study evaluated the levels of mitochondrial complex (I, II, II-III and IV) activity in lymphocytes from BD patients. We evaluated the following oxidative stress parameters: superoxide, thiobarbituric acid reactive species (TBARS) and carbonyl levels in submitochondrial particles of lymphocytes from bipolar patients. 51 bipolar patients were recruited into this study: 34 in the euthymic phase, and 17 in the depressive phase. Our results indicated that the depressive phase could increase the levels of mitochondrial superoxide, carbonyl and TBARS, and superoxide dismutase, and could decrease the levels of mitochondrial complex II activity in the lymphocytes of bipolar patients. It was also observed that there was a negative correlation between the Hamilton Depression Rating Scale (HDRS) and complex II activity in the lymphocytes of depressive bipolar patients. In addition, there was a positive correlation between HDRS and superoxide, superoxide dismutase, TBARS and carbonyl. Additionally, there was a negative correlation between complex II activity and oxidative stress parameters. In conclusion, our results suggest that mitochondrial oxidative stress and mitochondrial complex II dysfunction play important roles in the depressive phase of BD., (Copyright © 2018. Published by Elsevier B.V.)

Background: Ostomy is a surgical procedure that creates a stoma that aims to construct a new path for the output of feces or urine. The relationship of oxidative stress (OxS) markers in patients with ostomy is still poorly described., Objective: The present study was aimed at investigating the changes in oxidative stress parameters in peripheral blood collected from ostomy patients when compared with a healthy control group., Methods: It was evaluated 29 ostomy patients and 30 healthy control patients. The oxidative stress parameters evaluated were: lipid peroxidation [lipid hydroperoxide (LPO), 8-isoprostane (8-ISO) and 4-hydroxynonenal (4-HNE)], protein oxidation and nitration [carbonyl and 3-nitrotyrosine (3-NT)] and DNA oxidation [8-hydroxy-2'-deoxyguanosine (8-OHDG)] in serum from ostomy patients compared to health controls., Results: The data showed an increase of LPO, 8-ISO, 4-HNE, 3-NT and 8-OHDG in serum collected from ostomy patients when compared to healthy controls., Conclusion: The findings support the hypothesis that ostomy triggers the oxidative stress observed in the blood collected from these patients.

Bipolar disorder (BD) is a major health problem. It causes significant morbidity and imposes a burden on the society. Available treatments help a substantial proportion of patients but are not beneficial for an estimated 40-50%. Thus, there is a great need to further our understanding the pathophysiology of BD to identify new therapeutic avenues. The preponderance of evidence pointed towards a role of protein kinase C (PKC) in BD. We reviewed the literature pertinent to the role of PKC in BD. We present recent advances from preclinical and clinical studies that further support the role of PKC. Moreover, we discuss the role of PKC on synaptogenesis and neuroplasticity in the context of BD. The recent development of animal models of BD, such as stimulant-treated and paradoxical sleep deprivation, and the ability to intervene pharmacologically provide further insights into the involvement of PKC in BD. In addition, the effect of PKC inhibitors, such as tamoxifen, in the resolution of manic symptoms in patients with BD further points in that direction. Furthermore, a wide variety of growth factors influence neurotransmission through several molecular pathways that involve downstream effects of PKC. Our current understanding identifies the PKC pathway as a potential therapeutic avenue for BD.

Lithium (Li) is a mood-stabilizing drug used in the treatment of bipolar disorder (BD). Recently, preclinical studies have demonstrated the potential of tamoxifen (TMX) in the treatment of acute episodes of BD. However, the prolonged use of TMX for mood disorders treatment is controversial. In this study, we evaluated the effects of TMX or Li on cognitive behavior, as well as the levels of neurotrophic factors in the brain of male and female rats. Male and female Wistar rats received administrations of water (control group), TMX or Li via gavage for a period of 28days; the rats were then subjected to the open-field test (to evaluate spontaneous locomotion), and the novel object recognition and step-down inhibitory avoidance tests (to evaluate cognition). The levels of NGF, BDNF and GDNF were evaluated in the hippocampus and frontal cortex of the subject rats. No significant differences were observed in the open-field and inhibitory avoidance tests after drug administration in either the male or female rats. The administration of TMX, but not Li, decreased the recognition index of both the male and female rats in the object recognition test. The chronic administration of TMX decreased, whereas Li increased the levels of BDNF in the hippocampus of both the male and female rats. Tamoxifen decreased the levels of NGF in the hippocampus of female rats. In conclusion, it can be suggested that long-term treatments with TMX can lead to significant cognitive impairments by reducing the levels of neurotrophic factors in the brain of rats., (Copyright © 2017. Published by Elsevier Inc.)

Fenproporex (Fen) is an amphetamine-based anorectic; amphetamine use causes a broad range of severe cognitive deficits and anxiogenic-like effects. In this study we evaluated pharmacological effects of the chronic administration of Fen on cognitive and non-cognitive behaviors. Male adult Wistar rats received intraperitoneal administration of vehicle (control group) or Fen (6.25, 12.5 or 25 mg/kg) for 14 days; the animals were then subjected to habituation and object recognition tasks in open-field apparatus, and elevated plus-maze task. The administration of Fen (12.5 and 25 mg/kg) impaired habituation during the second exposure to the habituation task. In addition, the same doses of Fen also impaired the performance in object recognition task. In elevated plus-maze task, the administration of Fen (in all doses tested) induced anxiogenic-like effects in rats. Our results suggest that chronic Fen administration alters memory and induces anxiogenic-like effects in rats.

The aim of the present study was to evaluate the effects of sodium butyrate on depressive-like behavior and mitochondrial alteration parameters in animal models of depression induced by maternal deprivation or chronic mild stress in Wistar rats. maternal deprivation was established by separating pups from their mothers for 3 h daily from postnatal day 1 to day 10. Chronic mild stress was established by water deprivation, food deprivation, restraint stress, isolation and flashing lights. Sodium butyrate or saline was administered twice a day for 7 days before the behavioral tests. Depressive behavior was evaluated using the forced swim test. The activity of tricarboxylic acid cycle enzymes (succinate dehydrogenase and malate dehydrogenase) and of mitochondrial chain complexes (I, II, II-III and IV) was measured in the striatum of rats. From these analyses it can be observed that sodium butyrate reversed the depressive-like behavior observed in both animal models of depression. Additionally, maternal deprivation and chronic mild stress inhibited mitochondrial respiratory chain complexes and increased the activity of tricarboxylic acid cycle enzymes. Sodium butyrate treatment reversed -maternal deprivation and chronic mild stress- induced dysfunction in the striatum of rats. In conclusion, sodium butyrate showed antidepressant effects in maternal deprivation and chronic mild stress-treated rats, and this effect can be attributed to its action on the neurochemical pathways related to depression.

The neurobiological basis of bipolar disorder (BD) remains unknown; nevertheless, mitochondrial dysfunction has been identified in this disorder. Inactivation of any step in the tricarboxylic acid (TCA) cycle can impair mitochondrial ATP production. There is recent evidence indicating that PKC is an important therapeutic target for bipolar disorder. Therefore, we evaluated the effects of tamoxifen (TMX--a PKC inhibitor) on the activities of enzymes in the TCA cycle of rat brains subjected to an animal model of mania induced by amphetamine. In the reversal treatment, Wistar rats were first treated with d-AMPH or saliratsne (Sal) for 14 days. Thereafter, between days 8 and 14, the rats were administered TMX or Sal. The citrate synthase, succinate dehydrogenase, and malate dehydrogenase were evaluated in the frontal cortex, hippocampus, and striatum. The d-AMPH administration inhibited TCA cycle enzymes activity in all analyzed structures, and TMX reversed d-AMPH-induced dysfunction. In addition, we observed a negative correlation between d-AMPH-induced hyperactivity and the activity of these enzymes in the rat's brain. These findings suggested that TCA cycle enzymes inhibition can be an important link for the mitochondrial dysfunction seen in BD, and TMX exert protective effects against the d-AMPH-induced TCA cycle enzymes dysfunction., (© 2013 Published by Elsevier Ireland Ltd.)

Objective: To investigate the effects of cannabidiol (CBD) on mitochondrial complex and creatine kinase (CK) activity in the rat brain using spectrophotometry., Method: Male adult Wistar rats were given intraperitoneal injections of vehicle or CBD (15, 30, or 60 mg/kg) in an acute (single dose) or chronic (once daily for 14 consecutive days) regimen. The activities of mitochondrial complexes and CK were measured in the hippocampus, striatum, and prefrontal cortex., Results: Both acute and chronic injection of CBD increased the activity of the mitochondrial complexes (I, II, II-III, and IV) and CK in the rat brain., Conclusions: Considering that metabolism impairment is certainly involved in the pathophysiology of mood disorders, the modulation of energy metabolism (e.g., by increased mitochondrial complex and CK activity) by CBD could be an important mechanism implicated in the action of CBD.

Bipolar disorder is a severe mood disorder with high morbidity and mortality. Despite adequate treatment, patients continue to have recurrent mood episodes, residual symptoms, and functional impairment. Some preclinical studies have shown that histone deacetylase inhibitors may act on depressive-like and manic-like behaviors. Therefore, the aim of the present study was to evaluate the effects of sodium butyrate (SB) on behavioral changes in animal models of depression and mania. The animals were submitted to protocols of chronic mild stress or maternal deprivation for induction of depressive-like behaviors and subjected to amphetamine, or ouabain administration for induction of manic-like behaviors. SB reversed the depressive-like and manic-like behaviors evaluated in the animal models. From these results we can suggest that SB may be a potential mood stabilizer.

Several evidences have demonstrated that oxidative stress has a central role in bipolar disorder (BD). Recently, studies have been suggested histone deacetylases (HDAC) as a possible target for new medications in treatment of mood disorders. In this study, we investigated the effects of sodium butyrate (SB, a histone deacetilase inhibitor) on oxidative stress in rats submitted to an animal model of mania induced by d-amphetamine (d-AMPH). Wistar rats were first given d-AMPH or saline (Sal) for 14 days, and then, between days 8 and 14, rats were treated with SB or Sal. Locomotor activity and risk-taking behavior were assessed by open-field test and oxidative stress was measured in prefrontal cortex, amygdala, hippocampus and striatum. The results showed that SB reversed and prevented d-AMPH-induced behavioral effects. The d-AMPH administration induced oxidative damage in all brain structures analyzed. Depending on the cerebral area and technique, SB was able to reverse this impairment. The present study reinforces the need for more studies of HDAC inhibitors as possible target for new medications in treatment for BD., (Copyright © 2013. Published by Elsevier Ltd.)

Studies have shown alterations in mitochondrial complexes of bipolar disorder (BD) patients. However, changes in the Krebs cycle enzymes have been little studied. The animal model of mania induced by amphetamine has been widely used for the study of bipolar mania. The aim of this study is to assess behavioral and energy metabolism changes in an animal model of mania induced by methamphetamine (m-AMPH). Wistar rats were first given m-AMPH or saline for 14 days, and then, between days 8 and 14, rats were treated with lithium (Li), valproate (VPA), or saline (Sal). Locomotor behavior was assessed using the open-field task and activities of Krebs cycle enzymes (citrate synthase and succinate dehydrogenase), mitochondrial respiratory chain complexes (I, II, III, and IV), and creatine kinase measured in the brain structures (prefrontal, amygdala, hippocampus, and striatum). Li and VPA reversed m-AMPH-induced hyperactivity. The administration of m-AMPH inhibited the activities of Krebs cycle enzymes and complexes of the mitochondrial respiratory chain in all analyzed structures. Li and VPA reversed m-AMPH-induced energetic metabolism dysfunction; however, the effects of Li and VPA were dependent on the brain region analyzed. From the results obtained in this study, we suggested that the decreased Krebs cycle enzymes activity induced by m-AMPH may be inhibiting mitochondrial respiratory chain complexes. Therefore, changes in the Krebs cycle enzymes may also be involved in BD., (Copyright © 2012. Published by Elsevier Inc.)

Studies have demonstrated that AMPHs produce long-term damage to the brain dopaminergic, serotoninergic and glutamatergic regions. Prefrontal cortex, amygdala, hippocampus and striatum appear to be involved in the toxicity and behavioral changes induced by AMPHs. A single dose of AMPH causes mitochondrial dysfunction and oxidative stress in rat brain. The goal of the present study was thus to investigate the potency of two amphetamines, dextroamphetamine (d-AMPH) and methamphetamine (m-AMPH), on the behavior and energetic dysfunction in the brain of rats. d-AMPH and m-AMPH increased the crossing and rearing behaviors. The numbers of visits to the center were increased by d-AMPH and m-AMPH only at 2mg/kg. Likewise, at a high dose (2 mg/kg), the injection of m-AMPH increased the amount of sniffing. The AMPHs significantly decreased the activities of Krebs cycle enzymes (citrate synthase and succinate dehydrogenase) and mitochondrial respiratory chain complexes (I-IV); nevertheless, this effect varied depending on the brain region evaluated. In summary, this study demonstrated that at high doses, m-AMPH, increased stereotyped (sniffing) behavior in rats, but d-AMPH did not. However, this study shows that d-AMPH and m-AMPH seem to have similar effects on the brains energetic metabolism., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Recent studies have focused on the role of N-methyl-d-aspartate (NMDA) in brain injury. The present study is aimed at verifying memory, anxiety/depression parameters, and cellular viability in the brain of mice preconditioned with NMDA and subjected to the model of mild traumatic brain injury. For this purpose, male albino CF-1 mice were pre-treated with NMDA (75 mg/kg) and subjected to brain trauma, and after 24h submitted to memory tasks and anxiety and depression-like behavioral tests. The memory tests were evaluated at 1.5h, 24h, and 7 days after the training. In addition, the cellular viability was evaluated in the cerebral cortex and hippocampus 96 h after the trauma. It was observed that the cellular viability was reduced in the hippocampus of the mice subjected to trauma and the preconditioning with NMDA was able to protect this damage. All mice learnt the task in the habituation test, but in the object recognition task the mice preconditioned with NMDA were protected against impairment induced by TBI in both short and long-term memory. On the other hand, in the step-down inhibitory avoidance test, only the mice treated with NMDA showed impairment of long-term memory (7 days after training session). The evaluation of anxiety/depression behavior showed no changes after TBI. In conclusion, NMDA preconditioning induced impairment of the long-term memory; however, it was able to protect against the novel recognition memory impairment and increase the cellular survival in the hippocampus of mice exposed to traumatic brain injury., (Copyright © 2012 Elsevier B.V. All rights reserved.)