INCREASED WAKING AFTER INTRAACCUMBENS INJECTION OF M-CHLOROPHENYLBIGUANIDE - PREVENTION WITH SEROTONIN OR DOPAMINE-RECEPTOR ANTAGONISTS

Bilateral injection of the selective 5-HT3 receptor agonist m-chloroph enylbiguanide (5.0-40.0 mu g) into the nucleus accumbens of the rat si gnificantly increased waking and decreased slow wave sleep. Rapid eye movement (REM) sleep remained unchanged. Pretreatment with the 5-HT3 r eceptor antagonist MDL 72222 (1aH,3a,5a,H-tropan-3-yl-3,5-dichloro-ben zoate) (0.5 mg/kg s.c.) reversed the effects of m-chlorophenylbiguanid e (10.0-20.0 mu g) on sleep and waking. Blockade of the dopamine D-1 o r D-2 receptor with (+)-SCH 23390 (0.25 mg/kg s.c.) or YM-09151-2 n-3- yl)-5-chloro-2-methoxy-4-methylaminobenzamide) (0.5 mg/kg s.c.), respe ctively antagonized the increase of waking and reduction of slow wave sleep induced by m-chloro-phenylbiguanide (10.0 mu g). Our results ten d to indicate that the increase of wakefulness after injection of the selective 5-HT, receptor agonist m-chlorophenylbiguanide into the nucl eus accumbens is partly related to the release of endogenous dopamine. In addition, they suggest that concomitant stimulation of both accumb ens dopamine D-1 and D-2 receptor-related mechanisms is a necessary pr erequisite to increase wakefulness.