POSSIBLE INVOLVEMENT OF ALPHA(2)-ADRENOCEPTOR ON THE HYPNOTIC ACTION OF FLUNITRAZEPAM

This study examined whether the pharmacologic manipulation of catechol aminergic systems would affect the hypnotic action of flunitrazepam in rats. Flunitrazepam, a potent hypnotic, was used alone or in combinat ion with alpha-methyl paratyrosine (alpha MPT), an inhibitor of the sy nthesis of catecholamines, and clonidine (CLN), an alpha(2)-adrenocept or agonist. Flunitrazepam significantly increased the amount of slow-w ave sleep and the latency of paradoxical sleep (PS) and decreased the amount of PS. Administration of flunitrazepam to alpha MPT-treated rat s significantly increased the number of sleep cycles and PS episodes a s compared with flunitrazepam alone. Clonidine decreased total sleep t ime and significantly decreased PS. The association of flunitrazepam w ith CLN induced a decrease in PS and waking as compared with flunitraz epam alone. The possible involvement of noradrenergic mechanisms in mo dulating the effect of flunitrazepam on the rat sleep-waking cycle is proposed.