Increased waking after intra-accumbens injection of m-chlorophenylbiguanide: prevention with serotonin or dopamine receptor antagonists.
Bilateral injection of the selective 5-HT3 receptor agonist m-chlorophenylbiguanide (5.0-40.0 micrograms) 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-HT3 receptor antagonist MDL 72222 (1aH,3a,5a, H-tropan-3-yl-3,5-dichloro-benzoate) (0.5 mg/kg s.c.) reversed the effects of m-chlorophenylbiguanide (10.0-20.0 micrograms) on sleep and waking. Blockade of the dopamine D1 or D2 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 micrograms). Our results tend to indicate that the increase of wakefulness after injection of the selective 5-HT3 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 D1 and D2 receptor-related mechanisms is a necessary prerequisite to increase wakefulness.
Ponzoni
A
A
Department of Pharmacology and Therapeutics, School of Medicine, Clinics Hospital, Montevideo, Uruguay.
Monti
J M
JM
Jantos
H
H
Altier
H
H
Monti
D
D
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001645:Biguanides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D007267:Injections; D008297:Male; D009714:Nucleus Accumbens / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects; D014326:Tropanes / Q000494:pharmacology; D014851:Wakefulness / Q000187:drug effects*
D001549:Benzamides; D001552:Benzazepines; D001645:Biguanides; D018492:Dopamine Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014326:Tropanes; C065734:1-(3-chlorophenyl)biguanide; C042253:bemesetron; C030265:nemonapride