COMPARATIVE INVOLVEMENT OF 5-HT(1), 5-HT(2) AND 5-HT(3) 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 mug/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). These results suggest that, in rats, (i) 5-HT1 but not 5-HT2 and 5-HT3 receptors are involved in the mediation of emotional stress-induced stimulation of colonic motility and (ii) 5-HT1A receptor agonists inhibit stress-induced colonic disturbances by activating central cholecystokinin neurons through an afferent pathway from a peripheral site of action.