Cholecystokinin blockade of emotional stress- and CRF-induced colonic motor alterations in rats: role of the amygdala.
Intracerebroventricular (i.c.v.) injection of corticotropin-releasing factor (CRF) and emotional stress (ES) induce stimulation of colonic motility in rats, an effect blocked by i.c.v. injection of CCK-8s. This study examined in rats the contribution of the central nucleus of the amygdala (CA) in the blocking effect of CCK-8s on ES and CRF-induced colonic hypermotility. CRF (500 ng/kg, i.c.v.) induced a 73.5% increase in colonic spike burst frequency. Bilateral infusions of 1, 5, 10 and 20 ng/kg of CCK-8s in the CA region 10 min prior to CRF i.c.v. injection reduced, in a dose related manner, the CRF-induced stimulation of colonic motility. A 109% increase in colonic spike burst frequency was observed in rats placed in a test cage in which they had previously received electric footshocks (ES). CCK-8s and A-71623, a selective CCK-A receptor agonist, (10, 25 and 50 ng/kg) infused bilaterally into the CA, 30 min before ES, significantly reduced this stimulatory effect, while CCK-4 and A-63387, a selective CCK-B receptor agonist (10, 25 and 50 ng/kg), had no effect on such a response. CA lesions by ibotenic acid did not affect ES-induced increase in colonic spike activity. However, CCK-8s (50 ng/kg) microinfused into CA lesioned rats was unable to block the ES-induced stimulation of colonic motility, while CCK-8s i.c.v. injected (100 ng/kg) is still active on the colonic response to ES. These results suggest that CA is a site of interaction of CCK-8s with CRF to block the colonic response to stress and that these effects involve the CCK-A receptor subtype.(ABSTRACT TRUNCATED AT 250 WORDS)
Gué
M
M
Department of Pharmacology, INRA, Toulouse, France.
Tekamp
A
A
Tabis
N
N
Junien
J L
JL
Buéno
L
L
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003106:Colon / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007051:Ibotenic Acid; D007276:Injections, Intraventricular; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology*; D013315:Stress, Psychological / Q000503:physiopathology*; D013758:Tetragastrin / Q000031:analogs & derivatives / Q000494:pharmacology
D009842:Oligopeptides; D013758:Tetragastrin; C066278:A 71623; C075264:A 63387; D007051:Ibotenic Acid; D003346:Corticotropin-Releasing Hormone; D012844:Sincalide