Involvement of corticotrophin releasing factor (CRF) in the thermogenic and anorexic actions of serotonin (5-HT) and related compounds.
The present study investigated the involvement of corticotrophin-releasing factor (CRF) in the thermogenic and anorexic actions of serotonin (5-HT) in the rat. Serotonergic compounds and CRF antibody were injected directly into the third ventricle of conscious, male Sprague-Dawley rats. Thermogenesis was measured as changes in whole body oxygen consumption by indirect calorimetry. Central injections of 5-HT (0.5-50 micrograms, i.c.v.) significantly increased resting oxygen consumption (VO2; maximum 12.5% increase), without obvious effects on behaviour. Similar increases in VO2 (12-17%) were observed following central injections of the 5-HT precursors, tryptophan (14 micrograms, i.c.v.) or 5-hydroxytryptophan (5-HTP, 20 micrograms, i.c.v.), and peripheral (10 mg/kg, i.p.) or central (30 micrograms, i.c.v.) injections of the 5-HT reuptake inhibitor, DL-fenfluramine. Administration of a polyclonal CRF antibody (3 microliters, i.c.v.) 10 min prior to serotonergic compounds, significantly reduced (77-106%) the increases in VO2 observed in response to central injections of 5-HTP (20 micrograms), 5-HT (50 micrograms) or peripheral injections of fenfluramine, but not those observed in response to either 30 micrograms fenfluramine (i.c.v.) or 20 micrograms 5-HT. Voluntary food intake was measured for 6 h in rats following 16 h starvation. Six-hour food intake was significantly reduced (30-60%) in rats given central injections of 5-HT or 5-HTP, and central or peripheral injections of fenfluramine.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiological Sciences, University of Manchester, U.K.
R A
RA
Le Feuvre
L
L
Aisenthal
N J
NJ
Rothwell
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects*; D005277:Fenfluramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D014364:Tryptophan / Q000494:pharmacology
D005277:Fenfluramine; D012701:Serotonin; D014364:Tryptophan; D003346:Corticotropin-Releasing Hormone; D006916:5-Hydroxytryptophan