Increased waking after intra-accumbens injection of m-chlorophenylbiguanide: prevention with serotonin or dopamine receptor antagonists

• Published in: European journal of pharmacology 1995-05, Vol.278 (2), p.111-115
• Main Authors: Ponzoni, Ana, Monti, Jaime M., Jantos, Héctor, Altier, Humberto, Monti, Daniel
• Format: Article
• Language: English
• Subjects: (+)-SCH 23390; 5-HT 3 receptor; Animals; Benzamides - pharmacology; Benzazepines - pharmacology; Biguanides - administration & dosage; Biguanides - antagonists & inhibitors; Biguanides - pharmacology; Biological and medical sciences; Dopamine; Dopamine Antagonists - pharmacology; Injections; m-Chlorophenylbiguanide; Male; MDL 72222; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Nucleus Accumbens - physiology; Pharmacology. Drug treatments; Rats; Rats, Wistar; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - administration & dosage; Serotonin Receptor Agonists - pharmacology; Serotoninergic system; Sleep; Sleep - drug effects; Sleep, REM - drug effects; Tropanes - pharmacology; Wakefulness - drug effects; Waking; YM-09151-2
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(95)00108-W

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.