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 of diazepam on punished operant responding was studied in rats injected intracerebroventricularly with 150 microg 5,7-dihydroxytryptamine to deplete brain serotonin or pretreated with (S)-WAY 100135 (N-tert-butyl) 3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenylpropanamide dihydrochloride), an antagonist at 5-HT1A receptors. 5,7-Dihydroxytryptamine markedly depleted brain serotonin and caused a sustained increase in punished responding with no effect on rates of unpunished responding in sham-operated rats but had no effect in animals which had received 5,7-dihydroxytryptamine. At 5 and 10 mg/kg ipsapirone reduced unpunished responding 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 ipsapirone releases behaviour that is suppressed by punishment by stimulating presynaptic 5-HT1A receptors.
Cervo
L
L
Istituto di Richerche Farmacologiche Mario Negri, Milan, Italy.
Samanin
R
R
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011678:Punishment; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C081293:WAY 100135; D015116:5,7-Dihydroxytryptamine; C043077:ipsapirone; D003975:Diazepam