Studies on sleep/wake effects of serotonin reuptake inhibitors and receptor subtype involvement

Studies with the serotonin uptake inhibitors zimeldine and alaproclate show biphasic effects on the sleep/wake axis in rats and cats. Zimeldine induced an initial waking response succeeded by a small SWS-2 increase in rats. The waking increase was not blocked by the 5-HT2 antagonist ritanserin nor by the putative 5-HT1A antagonist (-)-alprenolol. In cats, zimeldine induced initial behavioural changes which were succeeded by a large SWS-2 increase. Alaproclate gave similar initial responses as zimeldine in both species, and was succeeded by a moderate sleep increase in cats but not in rats. The complex sleep/wake effects following the serotonin uptake inhibitors may result from simultaneous induction of incompatible serotonergic effects.