Buspirone inhibits corticotropin-releasing factor and stress-induced cecal motor response in rats by acting through 5-HT1A receptors.
The effect of buspirone on corticotropin-releasing factor (CRF) and stress-stimulated cecal motility and its antagonism by 5-HT1A (spiroxatrine) and sigma (BMY 14802) antagonists were evaluated by electromyography in rats equipped with chronically implanted electrodes on the cecum and a small catheter into the right lateral ventricle of the brain. Exposure to mental stress, consisting of a fear-conditioned response, increased during 30 min the frequency of cecal spike bursts significantly (P less than 0.01). The frequency of cecal spike bursts was also increased following intracerebroventricular injection of CRF (500 ng/kg). Buspirone (1 mg/kg s.c.) abolished the stimulatory effects of mental stress and CRF on cecal motility. Whereas spiroxatrine (0.5 mg/kg s.c.) blocked the effect of buspirone on the colonic hypermotility induced by i.c.v. injection of CRF, BMY 14802 at a similar dose (0.5 mg/kg s.c.) was unable to block the action of buspirone. It is concluded that s.c. administration of buspirone suppresses the stress-induced cecal motor response through 5-HT1A receptors, probably by inhibiting the central or peripheral pathways involved in CRF mediation of these effects.
Martinez
J A
JA
Department of Pharmacology, INRA, Toulouse, France.
Buéno
L
L
D000818:Animals; D002065:Buspirone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002432:Cecum / Q000187:drug effects* / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists; D004566:Electrodes; D004576:Electromyography; D005769:Gastrointestinal Motility / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D011619:Psychotropic Drugs / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D013141:Spiro Compounds / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology
D004146:Dioxanes; D018492:Dopamine Antagonists; D011619:Psychotropic Drugs; D011743:Pyrimidines; D011985:Receptors, Serotonin; D013141:Spiro Compounds; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; D003346:Corticotropin-Releasing Hormone; C018387:spiroxatrine; D002065:Buspirone; D004298:Dopamine