Comparative involvement of 5-HT1, 5-HT2 and 5-HT3 receptors in stress-induced colonic motor alterations in rats.
The role of 5-HT1, 5-HT2 and 5-HT3 receptors in the genesis of colonic motor alterations induced by emotional stress was evaluated in rats equipped with implanted nickel/chrome electrodes on the proximal colon and a catheter into the lateral ventricle of the brain. In control rats the frequency of colonic spike bursts increased from 7.6 +/- 1.3 to 16.8 +/- 1.3 per 10 min when the rats were placed in a test cage in which they had previously received electric footshocks. I.p. injection of methysergide (0.1 mg/kg) reduced by 54% the emotional stress-induced increase of colonic spike burst frequency, while a higher dosage (1 mg/kg) of methysergide had no effect. The i.p. injection of ketanserin (a 5-HT2 receptor antagonist, 0.1 and 1 mg/kg) or granisetron (a 5-HT3 receptor antagonist, 0.1 and 1 mg/kg) had no effect on emotional stress-induced colonic hyperkinesia. The i.p. injection of the 5-HT1A receptor agonists, buspirone (1 mg/kg) or 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino(tetralin) (0.05 and 0.1 mg/kg) or benzodiazepine (clonazepam, 1 mg/kg) significantly reduced or suppressed the emotional stress-induced increase of colonic spike bursts. Injected i.c.v., buspirone, but not 8-OH-DPAT, also reduced the emotional stress-induced hyperkinesia. Pretreatment with devazepide receptor (1 microgram/kg) antagonized the inhibitory effects of buspirone and 8-OH-DPAT injected i.p. on emotional stress-induced colonic hyperkinesia but did not alter the effects of clonazepam (1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Gué
M
M
Department of Pharmacology, INRA, Toulouse, France.
Alary
C
C
Rio-Lacheze
C D
CD
Junien
J L
JL
Buéno
L
L
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D058787:GABA-A Receptor Antagonists; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013315:Stress, Psychological / Q000378:metabolism
D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D017366:Serotonin Receptor Agonists; D002998:Clonazepam; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002065:Buspirone