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Investigation of the effects of Simvastatin on experimental psychosis models in mice Objective: Statins are potent inhibitors of cholesterol synthesis and are used in the prevention of coronary artery diseases. Evidence from clinical trials show other beneficial actions of statins not related to their cholesterol lowering effects. It was reported that simvastatin which is a statin agent, may alter dopaminergic functions via increasing the expression of dopamine D1 and D2 receptors in the rat prefrontal cortex. Dopaminergic overactivity is associated with schizophrenia. Additionally, it was observed that chronically administrated high dose (10mg/kg) of simvastatin induced an upregulation in the glutamate N-Methyl-D-aspartic acid (NMDA) receptors in rat brain and increased locomotor activity in rats. Glutamate depletion in brain contributes to the schizophrenia pathogenesis. This study aims to examine the chronic effects of simvastatin on experimentally induced psychosis models in mice. Materials and Methods: Male, Swiss albino mice were used in our study (n=112). Simvastatin was administered orally via gavage for 4 weeks at doses of 3, 10 ve 30 mg/kg (n=7). Saline was administered to control group for the same period (n=7). Apomorphine (dopaminergic receptor agonist)-induced climbing (AIC), haloperidol (dopaminergic receptor antagonist)-induced catalepsy (HIC) and dizocilpine (MK-801) induced hyperlocomotion (DIH) were used as psychosis models. The results of AIC and HIC were analyzed with Kruskal-Wallis test and the results of DIH was analyzed with One Way ANOVA. Results: There were no significant differences between groups in terms of climbing time in AIC, duration of cataleptic posture in HIC and total movements in DIH (p>0.05). Conclusion: We suggest that chronic administration of simvastatin do not possess antipsychotic effect at all doses when assessed with the above mentioned psychosis models. Simvastatin and control group did not differ in terms of the cataleptogenic effect.
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