The effects of selective activation of the 5-HT3 receptor with m-chlorophenylbiguanide on sleep and wakefulness in the rat.

The effects of the 5-HT3 receptor agonist, m-chlorophenylbiguanide, were compared with those of the 5-HT3 receptor antagonist, MDL 72222, in rats implanted with electrodes for chronic sleep recordings. m-Chlorophenylbiguanide (12.5-50.0 micrograms) injected into the left lateral ventricle increased wakefulness and rapid eye movement (REM) sleep latency, whereas slow wave sleep, REM sleep and the number of REM periods were reduced. MDL 72222 (0.1-1.0 mg/kg, s.c.) induced a delayed and dose-dependent increase of slow wave sleep. Pretreatment with MDL 72222 (0.1-0.5 mg/kg) prevented the effects of m-chlorophenylbiguanide (50 micrograms) on wakefulness and sleep. It is suggested that the increase of wakefulness after 5-HT3 receptor activation could be related to the release of endogenous serotonin and dopamine.