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    Agomelatine Protection in an LPS-Induced Psychosis-Relevant Behavior Model
    (Int Scientific Information, Inc, 2015) Inanir, Sema; Copoglu, Umit Sertan; Kokacya, Hanifi; Dokuyucu, Recep; Erbas, Oytun; Inanir, Ahmet
    Background: The aim of this study was to investigate the effect of agomelatine in a psychosis-relevant behavior model. Material/Methods: We used 18 adult male Wistar rats in this study. Twelve rats given LPS for endotoxemia were randomly divided into 2 groups (n=6). Group I was treated with 1 mL/kg 0.9% NaCl i. p. and Group II was treated with 40 mg/kg agomelatine. Six normal rats served as the control group and were not given LPS for endotoxemia. Cylindrical steel cages containing vertical and horizontal metal bars with top cover were used. Rats were put in these cages for the purpose of orientation for 10 min. Apomorphine was given to rats removed from cages, and then they were immediately put back in the cages for the purpose of observing stereotyped conduct. Brain HVA levels and plasma TNF-alpha levels were evaluated in tissue homogenates using ELISA. The proportion of malondialdehyde (MDA) was measured in samples taken from plasma for detection of lipid peroxidation similar to thiobarbituric acid reactive substances. Results: LPS induced-plasma TNF-alpha, brain TNF-alpha, and plasma MDA levels were significantly lower in the LPS+ agomelatine group compared to the LPS+ saline group (p< 0.05). HVA levels and stereotype scores were significantly lower in the LPS+ agomelatine group compared to the LPS+ saline group (p < 0.001). Conclusions: Agomelatine reduced TNF-alpha, HVA, MDA levels, and the stereotype score in relevant models of psychosis. Our results suggest that the anti-inflammatory effect of agomelatine involved oxidant cleansing properties and that its effects on the metabolism of dopamine can play an important role in the model of psychosis.
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    The Antipsychotic Effects of Omega-3 Fatty Acids in Rats
    (Elsevier Science Inc, 2015) Kokacya, Mehmet Hanifi; Inanir, Sema; Copoglu, Umit Sertan; Dokuyucu, Recep; Erbas, Oytun
    Background: In humans, omega-3 fatty acids are necessary for cell membranes, brain function and nerve transmission continuation. When animals are exposed to a new environment-or as a result of an apomorphine application that creates an agonistic effect on D1 and D2 receptors-they display behavioral reactions like rearing and stereotypy. This study aims to reveal the possible antipsychotic and oxidative effects of omega-3 fatty acids by comparing with chlorpromazine, a conventional antipsychotic drug, through evaluating the novelty-induced rearing and apomorphine-induced stereotypic behaviors, as well as malondialdehyde and glutathione levels in rats. Methods: Twenty-eight, adult, male, Wistar rats were used in the study. Briefly, 4 groups of rats (n = 7) were administered docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) (300 mg/kg; DHA: 120 mg/kg + EPA: 180 mg/kg intraperitoneally [IP]), DHA + EPA (150 mg/kg; DHA: 60 mg/kg + EPA: 90 mg/kg IP), chlorpromazine (1 mg/kg, IP) and isotonic saline (1 mL/kg, IP). One hour later, apomorphine (2 mg/kg, subcutaneously) was administered to each rat. After the apomorphine administration, rats were observed for stereotypic behavior. Results: This study shows that omega-3 fatty acids, similar to antipsychotics, reversed the psychotic like effects, increase of oxidants and decrease of antioxidants that are composed experimentally in rats. Conclusions: The application of omega-3 fatty acids has antipsychotic effects and causes an oxidative imbalance. This study adds new evidence to the current literature regarding the possible antipsychotic effects of omega-3 fatty acids.
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    Antipsychotic-like effect of minocycline in a rat model
    (E-Century Publishing Corp, 2014) Dokuyucu, Recep; Kokacya, Hanifi; Inanir, Sema; Copoglu, Umit Sertan; Erbas, Oytun
    Objectives: Tetracycline antibiotic drug minocycline has strongly neuroprotective and anti-inflammatory effects. Minocycline has also remarkable brain tissue penetration, is clinically entirely tolerated and properly absorbed when taken orally. In our study, we class with the effects of minocycline and chlorpromazine, a conventional antipsychotic drug, by evaluating the novelty-induced rearing, apomorphine-induced stereotypic behavior, and brain MDA levels in rats. Materials and Methods: Four groups of rat (n = 7) were applied with minocycline (50 and 100 mg/kg, i.p.), chlorpromazine (1 mg/kg, i.p.), or isotonic saline (1 mL/kg, i.p.). One hour later, apomorphine (2 mg/kg, s.c.) was applied to each rat. Result: Our results showed that both doses of minocycline significantly decreased the rearing behavior in rats, whereas the decrease with chlorpromazine was higher. Minocycline also decreased the stereotypy scores in a dose-dependent manner. Conclusion: We concluded that minocycline has beneficial effects on rearing behavior and stereotypy, which are accepted to be indicators of antipsychotic effect. Taken together, minocycline, as an anti-oxidant and cytoprotective agent, can be useful in neuroprotection especially on early stages of psychosis or prepsychotic patients with insignificant symptoms. Minocycline is worthy of being investigated for its anti-psychotic effects as a primary or an adjunctive drug.