Agomelatine Protection in an LPS-Induced Psychosis-Relevant Behavior Model.

BACKGROUND The aim of this study was to investigate the effect of agomelatine in a psychosis-relevant behavior model. MATERIAL AND 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-a 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-α, brain TNF-α, 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-α, 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.

Antipsychotic-like effect of minocycline in a rat model.

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.

Effects of paliperidone palmitate on coagulation: an experimental study.

OBJECTIVE: The aim of the present study was to examine the effects of a new antipsychotic drug paliperidone palmitate on hemogram and coagulation parameters in rats. MATERIALS AND METHODS: Experiments were performed on 22 female albino Wistar rats (8-12 weeks old). Control group was given drinking water as vehicle (0.3 mL). PAL-1 rats were given 1 mg/kg paliperidone palmitate (in 0.3 mL drinking water) by oral gavage once a day for ten days and PAL-3 rats received 3 mg/kg paliperidone palmitate (in 0.3 mL drinking water) by oral gavage for ten days. Blood samples were drawn from the heart 24 hours after the last drug dose, and hemogram and coagulation parameters were measured with automated analyzers. RESULTS: Hemogram did not change in the paliperidone treated groups compared to the controls. Factor VIII levels decreased in the PAL-1 and PAL-3 groups; and this decrease was significantly greater in the PAL-3. Factor IX levels decreased in PAL-3 rats, but its levels also increased in PAL-1 rats compared to the control. DISCUSSION: Paliperidone has led to changes in the serum levels of coagulation factors VIII and IX in rats. As a result, paliperidone may be causing thromboembolism or bleeding in a dose-independent manner.