Effects of olanzapine on ethanol withdrawal syndrome in rats

Abstract

The present study was designed to investigate the effects of olanzapine, a serotonin-dopamine antagonistic atypical antipsychotic agent, on ethanol withdrawal syndrome in rats. Adult male Wistar rats were subjects. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 21 days. Control rats were pair fed with an isocaloric liquid diet containing sucrose as a caloric substitute to ethanol. After 2nd, 4th and 6th h of ethanol withdrawal, rats were observed for 5 min, afterwards withdrawal signs that included locomotor hyperactivity, agitation, stereotyped behavior, tremor, wet dog shakes, abnormal posture and abnormal gait were recorded or rated. Olanzapine (0.5, 1 and 2 mg/kg) and saline were injected to the rats intraperitoneally 30 min before ethanol withdrawal assessment. A second series of injections was also given 30 rain before the 6th-h-observation, and subjects were then tested for audiogenic seizures. Olanzapine (2 mg/kg) produced significant inhibitory effects on stereotyped behaviors and wet dog shakes at the 6th h of ethanol withdrawal. Contrary, the same dose caused some increases in the intensity of posture and gait impairments at the 2nd h of ethanol withdrawal. In addition, that dose was found to be ineffective on agitation, tremor, tail stiffness and audiogenic seizures. Our results suggest that acute olanzapine treatment has beneficial effects on stereotyped behavior and wet dog shakes, but it also has some adverse effects on posture and gait during ethanol withdrawal in rats. Overall, olanzapine does not seem to be an adequate and suitable drug in controlling of ethanol withdrawal syndrome. (c) 2007 Elsevier B.V. All rights reserved.