Effects of risperidone, quetiapine and ziprasidone on ethanol withdrawal syndrome in rats

Comorbid substance use in schizophrenic patients is common, and substance dependence is a predictive factor for psychosis. The present study was designed to investigate the effects of risperidone, quetiapine and ziprasidone, atypical antipsychotic drugs, on ethanol withdrawal syndrome (EWS) in rats. Adult male Wistar rats were used in the study. Ethanol (7.2%, v/v) was given to rats via a liquid diet for 21days. An isocaloric liquid diet without ethanol was given to control rats. Risperidone (1 and 2mg/kg), quetiapine (8 and 16mg/kg), ziprasidone (0.5 and 1mg/kg) and vehicle were injected into rats intraperitoneally at 1.5 and 5.5h of ethanol withdrawal. At the 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5min, and withdrawal signs that included locomotor hyperactivity, stereotyped behaviors, abnormal gait and posture, tail stiffness and agitation were recorded or rated. Following the observations at the 6th hour, the rats were tested for audiogenic seizures. All three drugs had some significant inhibitory effects on EWS-induced behavioral signs beginning at the 2nd hour of withdrawal. The drugs also significantly reduced the incidence of audiogenic seizures. Overall, risperidone and quetiapine seemed to be more effective than ziprasidone in ameliorating the withdrawal signs. Doses of the drugs used in the present study did not produce any significant changes in locomotor activities of naïve rats. Our results suggest that risperidone, quetiapine and ziprasidone had beneficial effects on EWS in rats. Thus, these drugs may be helpful for controlling withdrawal signs in ethanol-dependent patients. ► Ethanol consumption for 21days caused physical dependence in rats. ► Risperidone, quetiapine and ziprasidone attenuated ethanol withdrawal syndrome. ► Effective doses of drugs did not affect locomotor activity of naïve animals. ► Risperidone and quetiapine seemed to be more effective than ziprasidone. ► These drugs may be helpful for controlling of ethanol withdrawal syndrome.