Effects of clozapine on ethanol withdrawal syndrome in rats.
OBJECTIVE
Co-morbid substance use in schizophrenic patients is common, and an important factor affects the outcome of disease. On the other hand, drug dependence is a predictive factor for psychosis. Alcohol is one of the most frequently abused psychoactive substances and may contribute psychotic symptoms in several conditions, such as withdrawal syndrome. The present study was designed to investigate the effects of clozapine on ethanol withdrawal syndrome (EWS) in rats.


METHODS
Adult male Wistar rats were used in the study. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 14 days. An isocaloric liquid diet without containing ethanol was also given to control rats. Clozapine (2.5, 5 and 10 mg/kg) and its vehicle (0.1% acetic acid) were injected to rats subcutaneously at the 1.5th and 5.5th hours of ethanol withdrawal. At 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min and withdrawal signs that included locomotor hyperactivity, agitation, tremor, tail stiffness, stereotyped behaviour and wet dog shakes were recorded or rated. Following the observations at 6th hour, subjects were tested for audiogenic seizures.


RESULTS
Clozapine significantly and dose-dependently inhibited the EWS-induced locomotor hyperactivity, wet dog shake, stereotyped behaviour, tremor and tail stiffness. However, it did not produce any significant effect on agitation and audiogenic seizures. Doses of clozapine used in the present study did not produce any significant change on locomotor activities of naïve rats.


CONCLUSIONS
Our results suggest that clozapine had some significant beneficial effects on EWS in rats. Thus, this drug may be helpful for controlling some withdrawal signs in ethanol-dependent patients.
Kayir
Hakan
H
Faculty of Medicine Department of Medical Pharmacology, Psychopharmacology Research Unit, Gulhane Military Medical Academy, Etlik 06018, Ankara, Turkey.
Uzbay
Tayfun
T
D000428:Alcohol Drinking / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use*; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology
D000431:Ethanol; D003024:Clozapine