PRESYNAPTIC 5-HT1A RECEPTORS MEDIATE THE EFFECT OF IPSAPIRONE ON PUNISHED RESPONDING IN RATS

The effect of ipsapirone, a partial agonist at 5-HT1A receptors, and o f diazepam on punished operant responding was studied in rats injected intracerebroventricularly with 150 mu g 5,7-dihydroxytryptamine to de plete brain serotonin or pretreated with (S)-WAY 100135 (N-tert-butyl 2-methoxyphenyl)piperazin-1-yl-2-phenylpropanamide dihydrochloride), a n antagonist at 5-HT1A receptors. 5,7-Dihydroxytryptamine markedly dep leted brain serotonin and caused a sustained increase in punished resp onding with no effect on rates of unpunished responding. Rates of puni shed responding returned to control values about 2 weeks after 5,7-dih ydroxytryptamine. At doses ranging from 2.5 to 10 mg/kg s.c. ipsapiron e significantly increased the rates of punished responding in sham-ope rated rats but had no effect in animals which had received 5,7-dihydro xytryptamine. At 5 and 10 mg/kg ipsapirone reduced unpunished respondi ng similarly in sham-operated and 5,7-dihydroxytryptamine-treated rats . Diazepam 2.5 mg/kg i.p. significantly increased punished responding and reduced rates of unpunished responding similarly in sham-operated and in 5,7-dihydroxytryptamine-treated animals. At 3 and 10 mg/kg (S)- WAY 100135 did not modify punished or unpunished responding but at 10 mg/kg it completely antagonized the effect of 5 mg/kg s.c. ipsapirone on unpunished and punished responding. The results suggest that ipsapi rone releases behaviour that is suppressed by punishment by stimulatin g presynaptic 5-HT1A receptors.