Effect of clozapine on the sleep pattern in the rat

The effect of clozapine on the sleep pattern in the rat was studied after a single injection (2.5--20 mg/kg) and after daily administration for 11 consecutive days (2 X 20 mg/kg/day). After a single injection clozapine significantly suppressed REM sleep in a dose-related way, leaving slow wave sleep (SWS) unchanged. Follwing chronic administration, however, clozapine exerted its most prominent effect on SWS, the enhancement of which persisted for at least 3 days after discontinuation of treatment. REM sleep decreased with the development of tolerance and in the absence of rebound phenomena. The results are discussed in the light of disturbances in brain monoamines and the tolerance these amines developed to repeated administration of clozapine.