Enhancement of 5-HT-induced anorexia: a test of the reversibility of monoamine oxidase inhibitors.
Subcutaneous injection of 1 mg/kg 5-hydroxytryptamine (5-HT) reduced the intake of a 10% sucrose solution in rats. A single injection of the monoamine oxidase inhibitor (MAOI) clorgyline enhanced the anorectic effect of 5-HT. Such an effect persists 2, 24, 48, 72 and 96 h after injection. The clorgyline treatment almost completely inhibited type A MAO activity in the liver at 2 h post-injection. By 120 h, the time at which potentiation of 5-HT induced anorexia disappeared, MAO-A activity had returned to 80% of control values. These results demonstrate that the clorgyline effect is long-lasting and irreversible. Brofaromine (5 mg/kg) and cimoxatone (20 mg/kg) also enhanced the anorectic effect of 5-HT injected 2 h later. The potentiating effects of brofaromine and cimoxatone were not observed when 5-HT was administered 24 h later. These results indicate that brofaromine and cimoxatone are short-acting, reversible inhibitors of MAO-A activity in vivo. Moclobemide (30 mg/kg) failed to enhance the anorectic action of 5-HT injected 2 and 24 h later. The potentiation of 5-HT induced anorexia may be a useful behavioural test for investigating the degree of reversibility, and time course of action of MAOIs.
Fletcher
P J
PJ
Neuropsychiatric Research Unit, University of Saskatchewan, Saskatoon, Canada.
Yu
P H
PH
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003010:Clorgyline / Q000494:pharmacology; D004357:Drug Synergism; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology; D023303:Oxazolidinones; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*
D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D010080:Oxazoles; D023303:Oxazolidinones; D010880:Piperidines; D012701:Serotonin; C038213:brofaromine; D003010:Clorgyline; D020912:Moclobemide; C026234:cimoxatone