Abstract
Bilateral injection of the selective 5-HT 3 receptor agonist m-chlorophenylbiguanide (5.0–40.0 μg) into the nucleus accumbens of the rat significantly increased waking and decreased slow wave sleep. Rapid eye movement (REM) sleep remained unchanged. Pretreatment with the 5-HT 3 receptor antagonist MDL 72222 (1 aH,3 a,5 a,H-tropan-3-yl-3,5-dichloro-benzoate) (0.5 mg/kg s.c.) reversed the effects of m-chlorophenylbiguanide (10.0–20.0 μg) on sleep and waking. Blockade of the dopamine D 1 or D 2 receptor with (+)-SCH 23390 (0.25 mg/kg s.c.) or YM-09151-2 ( cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide) (0.5 mg/kg s.c.), respectively antagonized the increase of waking and reduction of slow wave sleep induced by m-chloro-phenylbiguanide (10.0 μg). Our results tend to indicate that the increase of wakefulness after injection of the selective 5-HT 3 receptor agonist m-chlorophenylbiguanide into the nucleus accumbens is partly related to the release of endogenous dopamine. In addition, they suggest that concomitant stimulation of both accumbens dopamine D 1 and D 2 receptor-related mechanisms is a necessary prerequisite to increase wakefulness.
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