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Amaç: Gebelik sırasında sigara ve alkol tüketimi doğum eylemi üzerinde istenmeyen etkilere neden olmaktadır. Altta yatan mekanizmalar hala tam olarak anlaşılmamış olmakla birlikte, bozulmuş miyometriyum fonksiyonel yanıtları bu komplikasyonların nedenlerinden biri olabilir. Bu çalışmada, kronik sigara ve alkol tüketiminin izole term-gebe sıçan miyometriyum şeritlerinin fonksiyonel yanıtlarına etkisini araştırdık. Yöntem: 21 Wistar albino sıçanı üç gruba ayrıldı: Kontrol; Sigara grubu, sıçanlar 12 hafta boyunca sigara dumanına maruz kaldı; Alkol grubu, sıçanlara 12 hafta boyunca etanol uygulandı (n = 7, her bir grupta). Doğum dönemlerinde bulunan sıçanlardan izole edilen miyometriyal düz kas şeritleri, izometrik kayıt almak üzere organ banyosuna yerleştirildi. Karbakol (10-8-10-4 M), oksitosin (10-9-10-3 M) ve diltiazem (10-8-10-4 M) kümülatif konsantrasyonlarının miyometriyal spontan kasılmalar üzerindeki etkileri ölçüldü. Bulgular: Karbakol kasılma yanıtlarının amplitüd ve frekansları sigara grubunda anlamlı olarak artarken, alkol grubunda azaldı. Oksitosin ile indüklenen miyometriyal kasılmaların frekansı sigara maruziyetiyle artarken, kasılmaların amplitüdü değişmedi. Amplitüd ve frekans olarak oksitosin kasılmaları alkol grubunda azaldı. Her iki grupta da diltiazem gevşeme yanıtları arasında kontrollerine göre anlamlı olarak fark yoktu. Sonuç: Bu bulgular miyometriyal düz kasının kasılma ve gevşeme yanıtlarını değiştirmek yoluyla, sigara maruziyetinin erken doğuma neden olabileceğini ve alkol maruziyetinin gebelik süresini uzatabileceğini göstermektedir. Diltiazem gebelikte her iki durumda da tokoliz için yararlı bir etkiye sahip olabilir.

Obesity is associated with endothelial dysfunction and this relationship is probably mediated in part by inflammation. Objective: The current study evaluated the effects of etanercept, a tumor necrosis factor-alpha (TNF-α) inhibitor, on endothelial and vascular reactivity, endothelial nitric oxide synthase (eNOS) immunoreactivity, and serum and aortic concentrations of TNF-α in a diet-induced rat model. Design and results: Male weanling Wistar rats were exposed to a standard diet and cafeteria diet (CD) for 12 weeks and etanercept was administered during CD treatment. Isolated aortas of the rats were used for isometric tension recording. Carbachol-induced relaxant responses were impaired in CD-fed rats, while etanercept treatment improved these endothelium-dependent relaxations. No significant change was observed in papaverine- and sodium nitroprusside (SNP)-induced relaxant responses. eNOS expression decreased in CD-fed rats, but no change was observed between etanercept-treated CD-fed rats and control rats. CD significantly increased both the serum and the aortic levels of TNF-α, while etanercept treatment suppressed these elevated levels. CD resulted in a significant increase in the body weight of the rats. Etanercept-treated (ETA) CD-fed rats gained less weight than both CD-fed and control rats.

Chronic psychological stress may cause depression and it is a risk factor for vascular endothelial dysfunction. Inflammation may contribute to endothelial dysfunction. Resveratrol, which has antiinflammatory and vasculoprotective properties, has been reported its beneficial effects on endothelial dysfunction induced by hypertension, diabetes and, aging. The effects of resveratrol on stress-induced endothelial dysfunction is not investigated yet. This study aimed to investigate the efficacy of resveratrol on vascular function in the unpredictable chronic moderate stress (UCMS) model of rats and to examine the possible mechanisms of resveratrol by assessment of proinflammatory markers. Male rats were assigned to 4 groups (n = 8 for each group): Control, Control+Resveratrol, UCMS, UCMS+Resveratrol. UCMS and UCMS+Resveratrol groups were exposed to the UCMS procedure for 12 weeks. Resveratrol (20 mg/kg/day, i.p., during 12 weeks) was given to the Control+Resveratrol and UCMS+Resveratrol groups.Then depressive-like behaviors were evaluated by forced swimming test. After behavioral tests, systolic blood pressure was recorded. Endothelial function of the thoracic aorta was evaluated by isolated organ bath system. Vascular eNOS expression and inflammatory markers such as TNF-α, IL-1β, IL-6, CRP, ICAM1, MCP in serum and vascular tissue were analyzed to explore the mechanisms of resveratrol. UCMS resulted in depressive-like behavior, endothelial dysfunction and increased inflammatory cytokines in both serum and tissue samples. Resveratrol treatment improved depressive-like behavior, ameliorated vascular dysfunction, and reversed stress-induced inflammation. Our findings suggest that resveratrol exerted antidepressant-like effect and prevented vascular endothelial dysfunction by reducing systemic and peripheral inflammation in UCMS-induced depression in rats. Therefore, resveratrol may be a therapeutic option with a vasculoprotective effect in depression.

Objective: Studies on the actions of exogenous agmatine in experimental models have shown its anti-convulsant effects. However, there are no findings regarding the influence of agmatine on absence epilepsy. Therefore, we investigated the effects of the agmatine in the occurrence of spike-and-wave discharges (SWDs) in the Wistar Albino Glaxo Rijswijk rats (WAG/Rij) model of genetic absence epilepsy. Materials and Methods: Three different doses (20, 40 or 80 mg/kg) of agmatine or saline were administered intraperitoneally to the adult WAG/Rij rats, and electroencephalography (EEG) was recorded for 2.5 hours. The number and the mean and cumulative durations of SWDs were measured. The SWD frequency characteristics were quantified by means of average power-spectra of the first 2nd segments of the SWD complexes before and after the effective dose of agmatine. Results: Agmatine, administered 80 mg/kg systemically, temporarily increased the number and cumulative duration of SWDs compared with saline injected WAG/Rij rats. This effect of agmatine, however, was not associated with any change in the frequency characteristics of the SWD complexes. There was no effect on neither the incidence nor the cumulative duration of SWDs when agmatine administered in lower doses (20 or 40 mg/kg). Conclusion: Higher doses of agmatine temporarily and slightly increase the incidence of SWDs in WAG/Rij rats, which may suggest its possible aggravating activity in absence epilepsy patients through its activity on adrenergic, serotonergic and AMPA receptors., Amaç: Deneysel modellerde yapılan araştırmalar ekzojen agmatinin anti-konvülzan etkilerinin olduğunu göstermiştir. Ancak, agmatinin absans epilepsisi üzerindeki etkisine dair herhangi bir veri bulunmamaktadır. Bu çalışmada, agmatinin absans epilepsinin genetik bir modeli olan Wistar Albino Glaxo Rijswijk (WAG/ Rij) ırkı sıçanlarda Diken-ve-Dalga Deşarjlar (DDD) üzerine olan etkilerini araştırdık. Gereç ve Yöntem: Yetişkin WAG/Rij sıçanlarda periton içine 3 farklı doz agmatin (20, 40 ya da 80 mg/kg) ya da serum fizyolojik uygulandı ve 2,5 saat boyunca elektroensefalografi (EEG) kaydedildi. Elde edilen EEG kayıtlarında DDD’lerin sayısı, ortalama ve kümülatif süreleri değerlendirildi. DDD’lerin frekans özellikleri, etkili agmatin dozundan önce ve sonra, DDD aktivitesinin ilk iki saniyelik bölümlerinin ortalama güç spektrumları hesaplanarak karşılaştırıldı. Bulgular: WAG/Rij sıçanlara sistemik olarak uygulanan 80 mg/kg agmatin DDD’lerin sayısını ve kümülatif süresini serum fizyolojik uygulanan gruba göre geçici olarak arttırdı. Ancak, agmatinin bu etkisi DDD’lerin frekans özelliklerindeki bir değişiklikle ilişki bulunmadı. Daha düşük dozlarda uygulanan agmatin (20 or 40 mg/ kg) ise DDD’lerin sayı ve süresine değişikliğe yol açmadı. Sonuç: Yüksek doz agmatin WAG/Rij ırkı sıçanlarda DDD insidansını geçiçi olarak arttırmaktadır. Bu sonuçlar, agmatinin absans epilepsisi hastalarında adrenerjik, serotonerjik ve AMPA reseptörleri aracılığı ile olası bir kötüleştirici etki gösterebileceğini işaret etmektedir.

Essential tremor (ET) is one of the most prevalent movement disorders and the most common cause of abnormal tremors. However, it cannot be treated efficiently with the currently available pharmacotherapy options. The pathophysiology of harmaline-induced tremor, most commonly used model of ET, involves various neurotransmitter systems including glutamate as well as ion channels. Agmatine, an endogenous neuromodulator, interacts with various glutamate receptor subtypes and ion channels, which have been associated with its’ beneficial effects on several neurological disorders. The current study aims to assess the effect of agmatine on the harmaline model of ET. Two separate groups of male rats were injected either with saline or agmatine (40 mg/kg) 30 min prior to single intraperitoneal injection of harmaline (20 mg/kg). The percent duration, intensity and frequency of tremor and locomotor activity were evaluated by a custom-built tremor and locomotion analysis system. Pretreatment with agmatine reduced the percent tremor duration and intensity of tremor induced by harmaline, without affecting the tremor frequency. However, it did not affect the decreased spontaneous locomotor activity due to harmaline. This pattern of ameliorating effects of agmatine on harmaline-induced tremor provide the first evidence for being considered as a treatment option for ET.

We investigated the effect of resveratrol on endothelial and neuronal nitric oxide synthase (eNOS and nNOS) expression in the corpus cavernosum from chronic unpredictable mild stress (CUMS)-exposed rats in order to examine possible role of proinflammatory cytokines, which might play a role on erectile dysfunction (ED). Rats were randomly and equally divided into four groups such as control, control+resveratrol, CUMS and CUMS + resveratrol (20 mg/kg/day, i.p/8 weeks). Sucrose intake and forced swimming tests were used to evaluate depressive-like behaviors. nNOS, eNOS expressions, inflammatory markers, corticosterone and testosterone levels were analyzed either in blood samples and/or penile tissues. CUMS-exposed rats displayed depressive-like behaviors, reduced penile nNOS and eNOS expressions, and serum testosterone levels and enhanced serum and penile tissue levels of proinflammatory markers compared to controls. Resveratrol reversed depressive-like behaviors and suppressed serum and penile levels of proinflammatory markers, increased nNOS and eNOS expressions and testosterone levels in CUMS-exposed rats. Resveratrol exerted antidepressant-like effects and protected the development of CUMS-induced impairment of cavernosal eNOS and nNOS expressions associated with ED, which might be related to its anti-inflammatory action.

Erectile dysfunction (ED) has been reported to be associated with inflammation. This study investigated the effects of tumor necrosis factor alpha (TNF-α) inhibitor etanercept on penile neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) expressions, testosterone concentrations, neurogenic and endothelium-dependent relaxations of corpus cavernosum (CC), and circulating and cavernosal levels of inflammatory markers in aged rats. Animals were separated into control, aged, and etanercept-treated aged groups. Aged rats displayed significantly increased serum and cavernosal TNF-α, C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule (ICAM–1) levels, and decreased penile nNOS and eNOS expressions and serum testosterone levels compared with controls. In etanercept-treated aged group, NOS expressions were similar to that of the control group. The circulating and cavernosal concentrations of TNF-α, CRP, MCP-1, ICAM-1, and testosterone were also normalized by etanercept. Neurogenic and endothelium-dependent relaxant responses significantly decreased in aged rats and etanercept treatment markedly improved these relaxation responses. Our findings indicate that aging decreases penile NOS expression, neurogenic and endothelium-dependent relaxations of CC, and also suppresses serum testosterone levels by inducing inflammatory response that may contribute to the development of ED. TNF-α antagonism may be a novel strategy to treat aging-associated ED.

Chronic stress is an important public health problem known as a risk factor for depression, cognitive deficits, and also erectile dysfunction (ED). Resveratrol, a plant polyphenol, was reported to activate constitutive endothelial nitric oxide synthase (eNOS). Although resveratrol has been proven to exert beneficial effects on the unpredictable chronic mild stress (UCMS)-induced decline in cognitive functions, its potential protecting effect on the penile tissue subjected to UCMS was in fact not investigated. Therefore, restorative effects of resveratrol on neurogenic and endothelium-dependent relaxations were evaluated in the corpus cavernosum of rabbits exposed to UCMS. Eighteen male New Zealand white rabbits were assigned into three groups (n = 6 in each group): controls; UCMS; and UCMS rabbits treated with resveratrol (20 mg/kg/day, i.p.) for 12-week period of stress induction. UCMS was induced by a couple of defined adverse conditions applied in a shuffled order for 12 weeks. Neurogenic and endothelium-dependent relaxations of corpus cavernosum were assessed by using organ bath studies. Both the electrical field stimulation (EFS)-induced neurogenic and carbachol-induced endothelium-dependent relaxant responses significantly decreased in physiological stress and resveratrol treatment exhibited a marked improvement in these relaxation responses in vitro. Our results indicated that chronic psychological stress could lead to ED by reducing neurogenic and endothelium-dependent relaxations and resveratrol prevents impairment of the functional responses, suggesting a potential new treatment approach for treatment of ED during psychological stress.

Normal aging may lead to cognitive deficits, which is associated with endothelial dysfunction and neuroinflammation. Dysregulation of TNFα expression contributes to vascular aging and dementia. In this study, we investigated the effects of etanercept, which is a TNFα inhibitor, on cognitive and endothelial function in aged rats. Male Wistar albino rats were divided into 3 groups: Young (4 month), aged (24 month) aged+ETA (24 month+etanercept). Etanercept (0.8 mg/kg/weekly) was given to the aged+ETA group subcutaneously for 8 weeks. Then passive avoidance test (PAT) and the Morris water maze test (MWMT) were used to evaluate cognitive functions of rats. After the behavioral tests, the rats were subjected to systolic blood pressure (SBP) measurement, and then endothelial function of thoracic aorta was evaluated by isolated organ bath system. Thoracic eNOS expression, hippocampal BDNF expression and serum and hippocampal TNF levels were also measured. In aged rats, it was shown that cognitive performances in MWMT and PAT were abolished whereas SBP unchanged. Furthermore, aging resulted in endothelial dysfunction, decreased expressions of thoracic eNOS and hippocampal BDNF, and increased level of TNF in serum and hippocampus. In contrast, ETA improved age-related cognitive deficits and endothelial dysfunction. In addition, ETA reversed changes in protein expression in aged rats. The results of this study indicate that ETA prevents cognitive deficits, endothelial dysfunction, peripheral and neuro-inflammation and decreament of neurotrophin expression in aged rats. These findings suggest that ETA may be beneficial with neuroprotective and vasculoprotective effects in elderly patients.

Amac: Bu calismada, genetik absans epilepsili WAG/Rij sicanlarda kronik etosuksimid (ETS) tedavisinin absans nobetler ve gozlenebilecek olasi kardiyovaskuler degisiklikler uzerindeki etkilerinin arastirilmasi amaclanmistir. Gerec ve Yontem: Iki aylik erkek Wistar ve WAG/Rij sicanlar; Wistar kontrol, Wistar ETS, WAG/Rij kontrol ve WAG/Rij ETS gruplarina ayrilmistir (n=20). ETS gruplari 3 ay boyunca kronik ETS tedavisi (oral, 300 mg/kg/gun) almislardir. Uc aylik tedavi periyodunun sonunda EEG kayitlari kullanilarak diken dalga desarjlarinin (DDD) toplam sure, ortalama sure ve sayisi degerlendirilmistir. Ortalama arteriyel kan basinci (OAB) ve kalp hizi (KH) olcumleri gerceklestirilmistir. Bulgular: ETS tedavisi WAG/Rij sicanlarda DDD’leri toplam sure, ortalama sure ve sayi acisindan anlamli olarak azaltmistir. OAB, WAG/Rij kontrol grubunda Wistar kontrol grubuna gore anlamli olarak artmistir. KH, Wistar ETS grubunda Wistar kontrol grubuna gore anlamli olarak azalmistir. KCl aracili kasilma yanitlarinda Wistar kontrol grubuna gore Wistar ETS grubunda anlamli artma, WAG/Rij kontrol grubunda anlamli azalma saptanmistir. Sonuc: Sonuclarimiz OAB ve vaskuler reaktivitenin WAG/Rij sicanlarda arttigini gostermistir. ETS tedavisi, WAG/Rij sicanlarda kardiyovaskuler parametreleri degistirmezken Wistar sicanlarda KH ve vaskuler reaktiviteyi azaltmis OAB’yi etkilememistir. Bu degisikliklerde T-tipi Ca++ kanallarinin rol oynayabilecegi dusunulmektedir.

Chronic stress is associated with male sexual problems including ejaculatory dysfunctions. The aim of this study was to determine whether resveratrol (RS) or quercetin (QE) has protective effects on vas deferens (VD) contractility in the unpredictable chronic mild stress (UCMS) rat model of depression. Animals were separated into six groups: control, control + RS and control + QE, stress, stress + RS, and stress + QE. Stress groups were subjected to UCMS procedure for 5 weeks. Animals in treatment groups were injected intraperitoneally with RS (20 mg/kg) or QE (30 mg/kg) for 5 weeks during UCMS period. UCMS caused depressive-like behaviors and enhanced systemic levels of corticosterone. The nerve-evoked contractile responses of VD significantly impaired and, noradrenaline- and ATP-induced contractile responses of VD significantly increased in stressed rats. UCMS exposure also markedly enhanced oxidative stress and inflammation in VD tissues. Treatment with RS or QE significantly ameliorated all the aforementioned parameters. The current study demonstrated that RS or QE protected against chronic stress-induced VD dysfunction by their antioxidant and anti-inflammatory effects on VD, suggesting that oxidative stress and inflammation may be synergistic parts in the development of VD dysfunction associated with chronic stress-induced depression.

Objective NOD-like receptor protein 1 (NLRP1) inflammasome complex has been recently associated with chronic unpredictable mild stress (CUMS) model of depression. Our aim was to investigate whether ketamine-induced antidepressant effect is associated with suppression of NLRP1.Methods Wistar albino rats were divided into control, CUMS, CUMS+acute ketamine (a single 10 mg/kg dose) and CUMS+chronic ketamine (daily 10 mg/kg injections for 3 weeks) groups (n=10 for each group). Sucrose preference test and forced swimming test were performed to assess anhedonia and immobility time respectively for the severety of depression symptoms. Brain tissues were dissected and prefrontal cortex and hippocampus regions were used for real-time polymerase chain reaction (PCR) and immunohistochemical analysis.Results CUMS procedure significantly induced depressive-like symptoms whereas both acute and chronic ketamine treatment ameliorated them. mRNA expression levels of NLRP1, caspase 1, apoptosis-associated speck-like protein containing a CARD (ASC), NF-κB, endothelial nitric oxide synthase, IL-1β, IL-6, toll-like receptor 4 (TLR-4) and purinergic 2×7 receptor (P2X7R) and numbers of Iba- 1+and GFAP+glial cells were reduced by acute and/or chronic ketamine treatment.Conclusion In the present study for the first time upstream and downstream elements of the NLRP1 inflammasome complex are shown to be suppressed by ketamine thus reinforcing the involvement of NLRP1 in the physiopathology of depression.

Pro-inflammatory cytokines have been shown to be associated with the development of seizures in the WAG/Rij rat model of absence epilepsy. Importantly, WAG/Rij rats also exhibit cognitive deficits and depression-like behaviors. It is possible that pro-inflammatory cytokines mediate these comorbid conditions of absence epilepsy given their well-established effects on cognition and affective responses. The current study investigated the potential therapeutic effect of etanercept (tumor necrosis factor inhibitor) on cognitive impairment, depression-like behavior, and spike-wave discharges (SWDs) typically observed in the WAG/Rij rats. Eight-month-old male WAG/Rij rats and Wistar controls were tested in Morris water maze (MWM), passive avoidance (PA), forced swimming, sucrose preference, and locomotor activity tests, and electroencephalogram (EEG) recordings were taken from a separate group of WAG/Rij rats after 8 weeks of etanercept or vehicle treatment. Consistent with earlier work, WAG/Rij rats exhibited cognitive deficits and depression-like behavior. From these, the cognitive deficits and despair-like behavior were rescued by etanercept administration, which also reduced the frequency of SWDs without affecting their duration. Our results support the hypothesis that pro-inflammatory cytokines mediate the absence seizures and comorbid symptoms of absence epilepsy.

Purpose To determine whether resveratrol improves the adverse effects age on vascular function in mesenteric arteries (MAs), and diminishes the hyperactivity in adrenal gland with age. Methods Male F344 x Brown Norway rats were assigned to 6-month control (YC), 6-month resveratrol (YR), 24-month control (OC) and 24-month resveratrol (OR). Resveratrol (15 mg/kg) was provided to resveratrol groups in drinking water for 14 days. Results Concentration response curves to phenylephrine (PE, 10(-9)-10(-5)M), acetylcholine (Ach, 10(-9)-10(-5)M) and resveratrol (10(-8)-10(-4)M) were evaluated in pressurized isolated MAs. The Ach concentration-response curve was right shifted with maximal response diminished in OC compared with YC rats. These effects were reversed by resveratrol treatment. The resveratrol-mediated relaxant responses were unchanged with age or resveratrol suggesting an endothelium-independent mechanism. Resveratrol tended to increase endothelial nitric oxide synthase; caused no effect on copper-zinc superoxide dismutase; and normalized the age-related elevatation in DβH and NPY levels in adrenal medulla, two indicators of sympathetic activity. Conclusion These data indicate that resveratrol reverses age-related dysfunction in endothelium-dependent vasodilation in MAs and partially reverses hyperactivity of adrenomedullary function with age. This treatment may have a therapeuticpotential in the treatment of cardiovascular diseases or hypertension in the elderly.

OBJECTIVES: The impairment of cognitive functions in diabetes mellitus (DM) is well known. Nitric oxide (NO)-guanyly cyclase (GC)-cyclic guanosine monophosphate (cGMP) pathway is an important role in cognitive functions, and, consequently, phosphodiesterase-5 (PDE-5) inhibitors as well as NO-GC activators are of considerable interest in the treatment of cognitive deficits. Therefore, we aimed to investigate the effects of YC-1 (3-5-hydroxymethyl-2-furyl)-1-benzyl-indazole), an NO-GC activator, and zaprinast, a PDE-5 inhibitor, on cognitive dysfunction in streptozotocin (STZ)-induced diabetic rats. METHODS: Male Wistar rats were divided into five groups (nine rats in each): Control, Vehicle (DMSO), Diabetic (50 mg/kg/i.p. streptozotocin), Diabetic-YC-1 (1 mg/kg/day/i.p., for 4 weeks), and Diabetic-Zaprinast (10 mg/kg/day/i.p., for 4 weeks) group. The Morris water maze, passive avoidance, locomotor activity, and foot shock sensitivity tests were applied to assess the effect of YC-1 and zaprinast on learning and memory. To explore the mechanisms of YC-1 and zaprinast on learning and memory performance, protein expressions of brain-derived neurotrophic factor (BDNF) in hippocampus were examined immunohistochemically. RESULTS: Thirty days after the induction of DM, rats exhibited severe learning and memory dysfunctions associated with decreased BDNF expression. Both chronic YC-1 and zaprinast treatment improved cognitive performance and hippocampal BDNF expression in diabetic rats. In the locomotor activity and foot shock sensitivity test, no significant differences were observed between the groups. Furthermore, hyperglycaemia did not affect cognition enhancement effects of YC-1 or zaprinast in diabetic rats. CONCLUSIONS: Our findings highlight the beneficial effects of nitric oxide-guanylyl cyclase activators and PDE-5 inhibitors to improve cognitive function in diabetes.

31st Congress of the European-College-of-Neuropsychopharmacology (ECNP) -- OCT 06-09, 2018 -- Barcelona, SPAIN WOS:000458400500354 Background: Diabetes mellitus (DM) is associated with modest impairments in cognition. Common molecular pathways to cellular and metabolic dysfunction have been implicated in both DM and cognitive dysfunctions. It has been shown in rodent models that cognitive impairment might be an adverse effect of diabetes. These models are being increasingly used to study pathogenesis and to develop new treatments [1,2]. Agmatine is an endogenous guanidoamine produced from L-arginine in many organs, including brain. Studies suggest that agmatine could be regarded as a neurotransmitter and shown to facilitate memory and learning in rats, in scopolamine-induced amnesia, streptozotocin (STZ)-induced Alzheimer model and chronic stress-induced depression [3]. Hence, the present study was conducted to examine the effect of agmatine as a possible antidiabetic agent in STZ-induced diabetes mellitus (DM) model in rats by evaluating cognitive functions, molecular mechanisms of neuroinflammation and neuroplasticity besides histological changes due to astrosit/microglial activation. European Coll Neuropsychopharmacol

Aksöz, Elif (Balikesir Author), Background: Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. One of the most commonly prescribed oral antidiabetic drug, metformin, has been shown to have beneficial effects on restoring impaired cognitive function. In the present study, we investigated the effects of metformin on spatial memory in terms of alleviating scopolamine-induced learning and memory impairments in rats by using the Morris water maze (MWM) test and the modified elevated plus-maze (mEPM) test. Furthermore, we investigated the possible mechanisms of action of metformin in preventing cognitive dysfunction. Methods: Male Wistar rats received metformin (50, 100, or 200 mg/kg/day) via gavage feeding for three weeks. Scopolamine was administered intraperitoneally before the probe step of the MWM test or the acquisition session of the mEPM test. Results: The learning and memory impairment induced by scopolamine was reversed by metformin. In addition, metformin improved the level of phosphorylated AMP-activated protein kinase and cAMP responsive element binding protein. However, metformin pretreatment had no impact on inhibiting the scopolamine-induced changes in acetylcholine levels. Furthermore, metformin exerted its antioxidant effect by significantly reversing scopolamine-induced changes in malondialdehyde, total antioxidant status, and superoxide dismutase levels in the hippocampus. Conclusion: Our results indicate that one of the most commonly used antidiabetic drug, metformin, has the potential to prevent the development of dementia and be a novel therapeutic drug for the amelioration of cognitive dysfunction in AD., Balikesir University

Diabetes is one of the risk factors for the development of vascular dementia (VD), leading to endothelial dysfunction and cognitive impairment. Resveratrol has been shown to have antioxidant, antiinflammatory, and neuroprotective effects. The previous studies have also reported that resveratrol improves cognitive and vascular endothelial functions in several pathological conditions. In the present study we aimed to evaluate the effect of resveratrol on cognitive and vascular endothelial function and to explore the mechanisms of its effects in the streptozotocin-induced diabetic rat model of VD. Male Wistar rats were divided into 3 groups (n = 10 in each group): Control, diabetes (DM), DM + resveratrol (DM + RSV) groups. Rats from the DM + RSV group received resveratrol (20 mg/kg/day, ip) for 4 weeks after induction of diabetes and then cognitive functions of the rats were tested by the Morris water maze and a passive avoidance tests. After behavioral tests, endothelial function of thoracic aorta (the endothelium-dependent and -independent vasorelaxant responses) was investigated. To explore the mechanisms of resveratrol, endothelial eNOS, aortic superoxide dismutase (SOD), NADPH oxidase, heme oxygenase-1 (HO-1) levels, TNF-α and IL-1β expressions; serum SOD and NADPH oxidase levels and, hippocampal BDNF, TNF-α and IL-1β expressions were measured. It was shown that DM resulted in severe learning and memory deficits associated with endothelial dysfunction, increased expression of TNF-α and IL-1β, increased oxidative stress levels and decreased expression of eNOS and BDNF. In contrast, resveratrol treatment improved the cognitive decline. It was also found that chronic treatment with resveratrol ameliorated the impaired vascular reactivity. Reveratrol significantly reversed diabetes-induced changes of protein expression. Our data suggest that resveratrol prevents memory deficits, endothelial dysfunction, increased oxidative stress, inflammation and impairment of neurotrophin expression in a VD rat model. Thus, the vasculoprotective and neuroprotective effects of resveratrol may be beneficial in DM patients.

Psychological stress may lead to erectile dysfunction (ED), and inflammation has been evaluated as a major contributing factor. The goal of this study was to investigate the effects of etanercept (ETN), an anti-tumor necrosis factor α (TNF-α) protein, on cavernosal function in the unpredictable chronic mild stress (UCMS) rat model of depression. Animals were divided into 4 groups: animals not exposed to UCMS, animals not exposed to UCMS and treated with ETN, animals exposed to UCMS, and animals treated with ETN while exposed to UCMS. UCMS significantly impaired the neurogenic and endothelium-dependent relaxation responses; reduced cavernosal endothelial nitric oxide (NO) synthase (eNOS) and neuronal NO synthase (nNOS) expressions; decreased testosterone levels; enhanced systemic levels of corticosterone, TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule 1 (ICAM-1); and also increased cavernosal levels of TNF-α, IL-1β, and IL-6 in rats. ETN administration restored NO-mediated neurogenic and endothelium-dependent relaxation responses of the corpus cavernosum, increased cavernosal eNOS and nNOS expressions, enhanced testosterone levels, and decreased corticosterone levels in UCMS-exposed rats. Also, systemic inflammatory markers and cavernosal proinflammatory cytokine levels were reduced by ETN. Our results demonstrate the role of TNF-α-mediated inflammation in the development of depression and ED in rats exposed to chronic stress.

Objective: Purinergic 2X7 receptor (P2X7R) activation is known to be involved in pathogenesis of depression. Our aims were to investigate P2X7R-activated inflammasome pathways in parallel with induction of depression and to test the antidepressant-like effects of the selective P2X7R antagonist Brilliant Blue G (BBG) in a rat model of chronic unpredictable mild stress (CUMS). Methods: Male Wistar albino rats were divided into control, CUMS, CUMS+BBG25 (25 mg/kg/day) and CUMS+BBG50 (50 mg/kg/day) groups (n=10 for each group). Various stressors were applied to rats for 6 weeks to establish the CUMS model and daily BBG treatment was started at the end of 3rd week. Sucrose preference test and forced swim test (FST) were performed to assess antidepressant-like effects. Brain samples were obtained for real-time polymerase chain reaction and immunohistochemistry analysis. Results: In FST, duration of immobility was reduced in the CUMS+BBG50 group. Also, BBG treatment significantly enhanced sucrose preference. While NLRP3 gene expression levels were unchanged in rats exposed to the CUMS protocol, expression levels of other inflammasome pathway factors NLRP1, caspase-1, ASC, NF-kappa B, IL-1 beta, IL-6 and P2X7R were increased. BBG treatment reduced expression levels of these factors. Likewise, Iba-1 and GFAP immunoreactivities were enhanced by the CUMS protocol and this action was reversed by BBG treatment. Conclusion: Chronic administration of BBG in CUMS model results in antidepressant-like activity in a dose dependent manner. Molecular and histological results show that these effects might be at least partially related to the suppression of inflammasome-related neuroinflammatory responses and suggest involvement of NLRP1 in depression.

Since the discovery of nitric oxide (NO) as a neuronal messenger, its way to modulate learning and memory functions is subject of intense research. NO is an intercellular messenger in the central nervous system and is formed on demand through the conversion of L-arginine to L-citrulline via the enzyme nitric oxide synthase (NOS). Neuronal form of nitric oxide synthase may play an important role in a wide range of physiological and pathological conditions. Therefore the aim of this study was to investigate the effects of chronic 3-bromo 7-nitroindazole (3-Br 7-NI), specific neuronal nitric oxide synthase (nNOS) inhibitor, administration on spatial learning and memory performance in rats using the Morris water maze (MWM) paradigm. Male rats received either 3-Br 7-NI (20mg/kg/day) or saline via intraperitoneal injection for 5days. Daily administration of the specific neuronal nitric oxide synthase (nNOS) inhibitor, 3-Br 7-NI impaired the acquisition of the MWM task. 3-Br 7-NI also impaired the probe trial. The MWM training was associated with a significant increase in the brain-derived neurotrophic factor (BDNF) mRNA expression in the hippocampus. BDNF mRNA expression in the hippocampus did not change after 3-Br 7-NI treatment. L-arginine significantly reversed behavioural parameters, and the effect of 3-Br 7-NI was found to be NO-dependent. There were no differences in locomotor activity and blood pressure in 3-Br 7-NI treated rats. Our results may suggest that nNOS plays a key role in spatial memory formation in rats.

Introduction Diabetes is associated with anxiety and depression. Resveratrol, one of the most potent natural polyphenols with antioxidant properties, has been demonstrated to have benefits against diabetes. In the current study, we investigated the effects of resveratrol on depression and anxiety-like behaviors in diabetic rats. Methods Adult male Wistar albino rats were assigned for control and diabetic groups, and these groups were divided into four subgroups as follows: Saline-treated, DMSO-treated, resveratrol-treated and imipramine-treated animals (n=10). Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg), and 2 days after the STZ injection the rats having hyperglycemia (>300 mg/dl) were assigned to be diabetic. Rats in treatment groups were injected intraperitoneally with resveratrol (20 mg/kg) and imipramine (10 mg/kg) for 4 weeks. After 4-week-treatment period, tail suspension test (TST), forced swimming test (FST), elevated plus maze test (EPM) and locomotor activity test were performed. Blood samples were collected to estimate serum superoxide dismutase (SOD) and NADPH oxidase (Nox) levels. Results Diabetic rats displayed depressive-like behaviors in the FST and TST, and anxiety-like behaviors in the EPM. Resveratrol and imipramine decreased anxiety-like and depressive-like behaviors without affecting locomotor activity in diabetic rats. A significant reduction in SOD levels and a marked increase in Nox levels were observed in diabetic rats. Resveratrol treatment normalized these levels, while imipramine did not affect neither SOD nor Nox levels. Conclusion This study indicates that chronic resveratrol treatment may able to treat comorbid anxiety-and depressive-like behaviors in diabetes through inhibition of oxidative stress.

Objective: Biological aging has been recognized to cause impairment of memory and the development of vascular dementia. Based on our previous work, agmatine has been shown to have a beneficial effect and might have therapeutic potential on cognitive functions, including learning and memory. The aim of the present study was to examine the possible effect of agmatine on biological aging-induced vascular endothelial dysfunction and associated dementia in rats. Methods: We used three different age groups (4-month-olds, 18-month-olds and 24-montholds; n = 12 in each group) of control and agmatine-treated rats. Control animals received physiological saline for 8 weeks. Agmatine sulfate (40 mg/kg, twice daily) was given to the agmatine groups orally for 8 weeks. Herein, we investigated the effects of agmatine on systolic blood pressure (SBP), nitric oxide (NO)-mediated endothelium-dependent and - independent vasorelaxant responses in thoracic aorta, cognitive performance (passive avoidance test; PAT, and Morris water maze test; MWMT), endothelial nitric oxide synthase (eNOS) expression and both hippocampal and amygdaloid brain-derived neurotrophic factor (BDNF) expression in aged rats. Results: We found cognitive decline, endothelial dysfunction and reduced eNOS and BDNF expression in aged rats. All these changes may result from aging-induced vascular dementia. We also found that chronic treatment with agmatine may improve amygdala-dependent emotional and spatial learning and memorial performance, and endothelial function, and may regulate eNOS and BDNF protein expression in aged rats. Conclusion: Results of the current study point out that chronic agmatine treatment may prevent endothelial dysfunction associated with vascular dementia through eNOS and BDNF expression in aged rats. Gazi Universitesi Research Fund [01/2010-80] This study was supported by the Grant from the Gazi Universitesi Research Fund [project number: 01/2010-80] and presented at the 27th European College of Neuropsychopharmacology Congress, 18- 21 October 2014, Berlin, Germany. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. WOS:000403941900002 Q4

Background The aim of this study was to investigate the effects of a potent nitric oxide-guanylate cyclase activator, 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), on learning and memory functions in aged rats. Material/Methods Rats were divided into 2 groups as 4-month-old and 24-month-old rats. Rats received YC-1 (1 mg/kg/day) for 2 weeks long-term. Morris water maze (MWM) and passive avoidance (PA) tests were used to determine learning and memory functions. Results In the MWM test, there is a significant increase in the acquisition latency (1–4 days) of 24-month-old rats. There is a significant reduction in the “time spent in the escape platform’s quadrant” in 24-month-old rats compared to 4-month-old rats in the probe trial of the MWM test. YC-1 treatment reversed the reduction of the “time spent in the escape platform’s quadrant” of 24-month-old rats. In the PA test, there was no significant difference in the 1st-day latency of rats in all groups. On the 2nd day, retention latency significantly decreased in the 24-month-old rats compared to 4-month-olds. YC-1 reversed the diminished retention latency in 24-month-old rats. YC-1 treatment and aging did not affect results of the locomotor activity test or the foot-shock sensitivity test, suggesting our results were not due to a change in motor activity or disability of the animals. Conclusions Our findings suggest that activation of the NO-sGC-cGMP pathway plays an important role in spatial and emotional learning and memory functions in aged rats.

Aim: To investigate the effect of moderate alcohol consumption on metabolic alterations, inducible nitric oxide synthase (iNOS), immunohistochemical distribution, and morphological damage to penile erectile tissue in rats. Materials and methods: Male Wistar albino rats were divided into 2 groups. Group 1 rats (control group, n = 8) received tap water ad libitum, and group 2 rats (n = 8) were fed with 20% ethanol. Increasing levels of alcohol were given to the rats over 12 weeks. Immunohistochemistry was then performed using the avidin-biotin-peroxidase technique on 5-mu m thickness tissue sections. Stained sections were examined by imaging microscope. Results: Alcohol consumption resulted in a significant increase in iNOS immunoreactivity in the penile erectile tissue. Increased iNOS expression was determined in the tunica albuginea, cavernosal smooth muscle cells, trabeculae of connective tissue, arterioles, and the urethral epithelium. Moreover, chronic alcohol consumption resulted in decreasing serum testosterone and high density lipoprotein (HDL) levels with increasing cholesterol and triglyceride levels. Conclusion: Chronic moderate alcohol consumption can affect penile erectile tissue by increasing iNOS immunoreactivity and induce histopathological damage such as penile fibrosis. These abnormalities are also related to the defense mechanism against morphological damage. Kocaeli University, Kocaeli, TurkeyKocaeli University This work was supported by the Research Fund of Kocaeli University, Kocaeli, Turkey.

Sexual dysfunction is a common and underestimated effect of antidepressants. However, the mechanism by which these drugs cause erectile dysfunction is unclear. We investigated the reactivity of the corpus cavernosum of rabbits that were treated with either chronic imipramine, which is a tricyclic agent; agomelatine, which is a melatonergic agonist and serotonin 5HT(2c) antagonist; or moclobemide, which is a reversible inhibitor of monoamine-oxidase A. Twenty rabbits were randomly divided into four groups: the control group (n=5), the imipramine-treated group (n=5), which received i.p. injections of 10 mg/kg/day of imipramine, the moclobemide-treated group (n=5), which received i.p. injections of 20 mg/kg/day of moclobemide, and the agomelatine-treated group (n=5), which was orally administered 10 mg/kg/day of agomelatine. The reactivities of corpus cavernosum tissue obtained from the antidepressant-treated and the control groups were studied in organ chambers after the animals were subjected to 21 days of drug administration. The acetylcholine-induced endothelium-dependent and the electrical field stimulation (EFS)-induced neurogenic relaxation of the corpus cavernosum of the imipramine-treated group was significantly decreased compared with the control group. However, neither the acetylcholine- nor EFS-induced relaxation was changed in the moclobemide- or agomelatine-treated groups. There were no change in the relaxant response to the nitric oxide (NO) donor sodium nitroprusside and contractile response to KCl between the groups. This study suggests that chronic imipramine treatment but not agomelatine and moclobemide treatments causes significant functional changes in the penile erectile tissue of rabbits and that these changes may contribute to the development of impotence.

article i nfo Our aim was to investigate the effects of acute harmane administration upon learning and memory perfor- mance of rats using the three-panel runway paradigm and passive avoidance test. Male rats received harmane (2.5, 5, and 7.5 mg/kg, i.p.) or saline 30 min. before each session of experiments. In the three panel runway paradigm, harmane did not affect the number of errors and latency in reference memory. The effect of harmane on the errors of working memory was significantly higher following the doses of 5 mg/kg and 7.5 mg/kg. The latency was changed significantly at only 7.5 mg/kg in comparison to control group. Animals were given pre-training injection of harmane in the passive avoidance test in order to deter- mine the learning function. Harmane treatment decreased the retention latency significantly and dose de- pendently, which indicates an impairment in learning. In this study, harmane impaired working memory in three panel runway test and learning in passive avoidance test. As an endogenous bioactive molecule, harmane might have a critical role in the modulation of learning and memory functions.

Objective: Agmatine, the decarboxylation product of arginine produced by arginine decarboxylase, is a novel neurotransmitter and exists in the mammalian brain. Agmatine has been reported to modulate cognitive functions, including learning and memory. Methods: In the present study, we evaluated the effects of agmatine on cognitive performance and oxidative damage in intracerebroventricular (i.c.v.) streptozotocin (STZ) model of Alzheimer's disease (AD). Adult male Sprague-Dawley rats were injected STZ (3mg/kg, i.c.v, bilaterally) on days 1 and 3. The learning and memory patterns were assessed by using passive avoidance, Morris water maze, and closed field activity tests. Also, malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activity have been determined as the parameters of oxidative damage. The behavioral tests were performed after 14 days from the first injection of STZ. Rats with impaired learning and memory performance were treated with intraperitoneal (i.p.) agmatine (40 mg/kg) twice daily for 7 days. After agmatine treatment, rats were subjected to the aforementioned behavioral tests again. Immediately after decapitation of the rats, the brains were collected and analyzed for oxidative damage parameters. Results: Agmatine improved the STZ-induced both spatial and emotinal memory impairment and oxidative damage. Findings of the study demonstrated the effectiveness of agmatine in reversing the cognitive deficits as well as the oxidative damage caused by i.c.v STZ. Conclusion: Taken together, our results have provided experimental evidence suggesting a possible therapeutic potential of agmatine as a regulator in etiopathogenesis of neurodegenerative diseases such as Alzheimer's disease.

Agmatine (l-amino-4-guanidino-butane), a metabolite of L-arginine through the action of arginine decarboxylase, is a novel neurotransmitter. In the present study, effects of agmatine on cognitive functions have been evaluated by using one trial step-down passive avoidance and three panel runway task. Agmatine (20, 40, 80 mg/kg i.p.) was administered either in the presence or absence of a cholinergic antagonist, scopolamine (1 mg/kg i.p.). Scopolamine significantly impaired learning and memory in both passive avoidance and three panel runway test. Agmatine did not affect emotional learning, working and reference memory but significantly improved scopolamine-induced impairment of learning and memory in a dose dependent manner. Our results indicate that agmatine, as an endogenous substance, may have an important role in modulation of learning and memory functions.

The aim of this study was to compare the effects of both neuronal NOS (nNOS) and inducible NOS (iNOS) inhibitor 2-iminobiotin, with the more selective nNOS inhibitor N(ω)-propyl-L-arginine (NPLA) and selective inducible NOS (iNOS) inhibitor aminoguanidine, on emotional learning, working memory and reference memory, by using three panel runway and passive avoidance paradigm in order to clarify the role of distinct isoforms of NOS in the regulation of learning and memory functions. NPLA and 2-iminobiotin significantly increased the number of errors and latency of working and reference memory performances of rats in three panel runway paradigm and impairs retention for the passive avoidance task. However, aminoguanidine did not affect cognitive functions in three panel runway and passive avoidance test. The effect of NPLA and 2-iminobiotin was reversed by pretreatment with a NOS substrate L-arginine. In conclusion, NPLA and 2-iminobiotin impaired cognitive functions in different kind of tasks used in this study and the effect of NPLA and 2-iminobiotin was found to be NO-dependent. Our results may confirm that nNOS plays the key role on emotional learning, working memory and reference memory in rats.

Trace elements have an important effect on and play a key role in a variety of the processes necessary for life. Studies have indicated a definite correlation between content of trace elements and many common diseases. It has been concluded that smoking may be a substantial source of intake of these hazardous elements, not only to the smoker, but to nonsmokers via passive smoke, as well. Even passive intake of such elements can change the metabolism of other trace elements and influence their concentrations. In order to assess their potential role in some human diseases, it is necessary to measure trace element concentrations in various tissues in experimental models. In this study, liver, kidney and spleen tissue samples from rats exposed to secondhand smoke were analysed for Fe, Cu, Zn, Cr, Mn and Co trace element levels by atomic absorption spectrophotometer. Cr, Mn, Fe and Co levels in the liver, Fe and Co levels in the kidney, and Zn, Cu, Mn and Co levels in the spleen were significantly lower than those of controls, but Cu levels in the kidney and Fe levels in the spleen were significantly higher than those of controls. Our data suggest that chronic exposure to cigarette smoke alters the trace element concentration of various tissues in rats exposed to secondhand smoke. These alterations may be attributable to oxidative stress produced by cumulative effect of inhaled smoke rather than the toxic effect of absorbed toxic metals. Low Mn levels in the liver and spleen, increased Cu levels in kidney and Fe levels in the spleen, and changes in the metabolism of Zn, Fe and Cu may be indicators of oxidative stress. Decreases in Co and Cr levels in rats exposed to secondhand smoke may also be related to the intake of the toxic trace elements present in cigarette smoke. [Med-Science 2012; 1(1.000): 1-12]

ObjectivePurinergic 2X7 receptor (P2X7R) activation has recently been considered to be involved in depression at least partially by triggering microglial activation. The aim of the present study was to examine whether the chronic administration of brilliant blue G (BBG), a highly selective P2X7R antagonist, has antidepressant-like effects and microglial (Iba-1) immunoreactivity in chronic unpredictable mild stress (CUMS) model in rats.MethodsMale Wistar Albino rats (290–360 g) were divided into groups such as control (saline), CUMS, CUMS + Imipramine (20 mg/kg; i.p.), CUMS + BBG25 (25 mg/kg; i.p.), CUMS + BBG50 (50 mg/kg; i.p.) groups (n = 10–12 in each). In CUMS model, various stressors were applied for 40 days. On day 20, the treatment of BBG was started for 20 days. At the end, sucrose preference and forced swimming tests were performed. Then brains were removed with paraformaldehyde perfusion for Iba-1 immunohistochemical analysis in hippocampus. One-way analysis of variance and Tukey's test were used for statistical analysis.ResultsThe time of immobility in forced swim test was significantly reduced while sucrose preference was increased in Imipramine and CUMS + BBG50 groups compared to control and CUMS groups, respectively. In immunohistochemical experiments, Iba-1 was overexpressed in CUMS group and BBG significantly reduced the overexpression of Iba-1.ConclusionOur results suggest that chronic administration of BBG has an antidepressant-like activity supporting the notion of P2X7 receptors involvement in depression by modulating microglial activation.This research was supported by grant from Marmara University, Scientific Research Projects – SAG-C-YLP-110915-0416 and SAG-E-120613-0233.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The effects of dextromethorphan (DM, CAS 6700-34-1), a common over-the-counter cough suppressant, on the reference memory have been investigated by a three-panel runway setup in rats. This study was designed by using a repeated acquisition procedure such as a radialarm maze task or a water maze task. DM (20-40 mg/kg i.p.) produced a significant decrease in the number of errors (pushes made on the two incorrect panels of the three panel gates at four choice points) and latency. Systemically administered scopolamine (CAS 114-49-8) (1 mg/kg i.p.) impaired the performance on both parameters. DM (40 mg/kg i.p.) was effective in reversing the reference memory deficit induced by administration of scopolamine. DM acts as a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors. Our results suggest that inhibition of NMDA receptors by DM supports its potential positive properties. This finding might present an oppurtunity for the evaluation of this old antitussive drug.

Resveratrol (3,5,4-trihydroxy-trans-stilbene), which is found in grapes and red wine has been shown to protect neuronal cells with its antioxidant activity, improve memory function in dementia and reverse acetylcholine esterase (AChE) activity. The aim of this study was to investigate the effect of resveratrol on emotional and spatial memory in naive rats, as well as on scopolamine- and mecamylamine-induced memory impairment in the passive avoidance and Morris water maze (MWM) tests. Resveratrol (12.5, 25 and 50 mg/kg), scopolamine (0.6 mg/kg) and mecamylamine (10mg/kg) were administered to male Wistar rats. In the passive avoidance test, there was no significant difference in the first day latency between all groups, whereas scopolamine and mecamylamine significantly shortened the second day latency compared to the control group. Resveratrol reversed the effect of scopolamine at all doses used, but it had no effect on mecamylamine-induced memory impairment in the passive avoidance test. Both scopolamine and mecamylamine significantly decreased the time spent in the escape platform quadrant during the probe trial of the MWM test compared to the control group. Resveratrol reversed the effect of scopolamine at all doses, but did not change the effect of mecamylamine in the MWM test. There were no significant differences in the locomotor activities of any of the groups. In conclusion, we suggested that resveratrol had improving effects on learning and memory by acting on muscarinic cholinergic receptors and at least in part, may reverse AChE activity.