No abstract

Schizophrenia is known to be associated with metabolic disturbances including diabetes mellitus, obesity and cardiovascular diseases. A growing body of evidence has suggested abnormal cytokine levels in schizophrenia. In the present study, we explored the effects of low-grade chronic inflammation on behavioral stereotypy in a rat model of non-alcoholic fatty liver disease (NAFLD). In order to induce NAFLD, rats were fed with either water enriched with 30 % fructose or plain tap water for 8 weeks. Following feeding period, behavioral stereotypy was evaluated with apomorphine-induced stereotypy test. Also, levels of tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2) and nuclear factor kappa B (NF-κB) in the liver and brain tissues were assessed biochemically. Brain homovanilic acid (HVA) was measured to evaluate the dopamine turnover. NAFLD rats showed significantly higher stereotypy score compared to controls (p = 0.016). TNF-α, IL-2, and NF-κB levels were significantly increased in NAFLD rats compared to control group. Brain HVA levels were elevated in NAFLD rats as well (p = 0.008). Moreover, NAFLD group prompted a considerable increase in brain IL-2 immunoexpression (p = 0.005). In conclusion, the present study demonstrates that low-grade chronic inflammation such as NAFLD may enhance apomorphine-induced stereotypic behavior via increasing dopaminergic activity in rats.

Trimetazidine (TMZ) has been used as an anti-ischemic agent for angina pectoris, chorioretinal disturbances, and vertigo. Also, it can induce extrapyramidal type adverse reaction such as parkinsonism, gait disorder, and tremor via blockade of D2 receptors. In the present study, we evaluated the effect of TMZ on novelty-induced rearing behavior and apomorphine-induced stereotypy behavior in male rats. Four groups of rat (n = 7) were administrated with TMZ (10 and 20 mg/kg, i.p.), chlorpromazine (1 mg/kg, i.p.), or isotonic saline. One hour later, apomorphine (2 mg/kg, s.c.) was administrated to each rat. Our results showed that both doses of TMZ significantly decreased the rearing behavior in rats, whereas the decrease with chlorpromazine was higher. TMZ also decreased the stereotypy scores in a dose-dependent manner. We concluded that TMZ has beneficial effects on rearing behavior and stereotypy, which are accepted to be indicators of antipsychotic effect. Taken together, with its antioxidative and cytoprotective properties, TMZ is worthy of being investigated for its anti-psychotic effects as a primary or an adjunctive drug.

Introduction: In contrast to several studies that examined different domains of neurocognitive functions in long-term abstinent cannabis users, there are few studies examined impulsivity in cannabis users with prolonged abstinence. The aim of this study was to test whether impulsivity and sensation seeking traits and impulsive decision-making are transient or enduring in patients with cannabis dependence who were abstinent for at least 1 month. Methods: The study included 30 patients with cannabis dependence (CDP) who had been abstinent for at least 1 month and 30 healthy controls. All the participants were male and the two groups were matched for age and duration of education. Results: As a result of Iowa Gambling Task (IGT) evaluation, there was no significant group (CDP vs. control) by block interaction in IGT performance (p=0.680). CDP showed significantly higher Barratt Impulsiveness Scale-11 (BIS-11) total (p=0.006), BIS-11 non-planning (p=0.006) and Zuckerman Sensation Seeking Scale experience seeking subscale (p=0.001) scores compared with controls. Conclusions: This is the first study to investigate decision-making, selfreport impulsivity and sensation seeking in long-term abstinent CDP. Our findings suggest that both self-report impulsivity and experience seeking may reflect a stable trait in CDP but not deficits on decisionmaking. This suggestion is consistent with the hypothesis that elevated impulsivity and sensation seeking traits may lead to addiction when they occur together rather than alone.

Although understanding the relation between psychotic behavior and immune abnormalities has been the focus of research for many years, it remains to be elucidated whether the changes in cytokine levels are part of etiology or a result of the stress associated with the disorder. In accordance with previous studies on changes in cytokine levels due to metabolic changes and psychosis, we hypothesized that fatty liver may potentiate apomorphine-induced stereotypy in a rodent model and that a synthetic glucagon-like peptide-1 analog exenatide would ameliorate this effect. In this study, 18 male Sprague Dawley albino mature rats were used. We induced hepatosteatosis in these rats by feeding them with 30% fructose dissolved in drinking water for 8 weeks. The animals were divided into three groups, namely, the normal group, the intracerebroventricular (ICV) exenatide group, and the ICV NaCl group. Apomorphine-induced stereotypic behavior test was performed in all groups and the liver was removed for histopathological examination after all the rats were euthanized. In the nonalcoholic fatty liver (NAFL) group, stereotypy scores were significantly increased compared with the control group rats (p < 0.00001). A significant decrease in stereotypy scores were observed in the ICV exenatide group with NAFL when compared with the ICV saline group with NAFL (p < 0.005). In addition, brain malondialdehyde and tumor necrosis factor-α levels decreased in the ICV exenatide group. The results of this study showed that fatty liver enhances the effect of apomorphine on stereotypy, which was reversed by exenatide possibly by antioxidant and anti-inflammatory effects.

Antipsychotic-like effect of agomelatine in a rodent modelObjective: Agomelatine is a naphthalene bioisostere of melatonin. Melatonin is involved in several neurophysiological systems; nevertheless, data about the relationship between melatonin and psychosis such as schizophrenia are limited and contradictory. In this study, we examined the antipsychotic-like effects of agomelatine in a rodent model. Method: In this study, we evaluated the effect of agomelatine on novelty-induced rearing behavior and apomorphine-induced stereotypical behavior in male rats. Agomelatine (20 and 40mg/kg, i.p.), chlorpromazine (1mg/kg, i.p.), or isotonic NaCl (1mL/kg, i.p.) were administered to four groups of rats (n=6), respectively. An hour later, apomorphine (2mg/kg, s.c.) was administered to each rat. Results: Our results showed that either dose of agomelatine decreased rearing behavior in rats significantly, in a dose dependent manner. Agomelatine also decreased the stereotypical behaviour scores like chlorpromazine did. Conclusion: We conclude that agomelatine has beneficial effects on rearing and stereotypical behaviour, which were accepted to be indicators of antipsychotic effect.