5-HT1A receptor full and partial agonists and 5-HT2C (but not 5-HT3) receptor antagonists increase rates of punished responding in rats.
Drugs with different intrinsic activity at 5-HT1A receptors and antagonists at 5-HT2A/2C and 5-HT3 receptors were studied for their ability to increase the rates of punished operant responding in rats. Like chlordiazepoxide (5 and 10 mg/kg) and diazepam (1.25 and 2.5 mg/kg), 0.125 mg/kg 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, and 5 and 10 mg/kg ipsapirone, a partial agonist at these receptors, increased the rates of punished responding, whereas (S)-WAY 100135, a 5-HT1A receptor antagonist, had no effect at doses from 1 to 10 mg/kg. 8-OH-DPAT and ipsapirone, like benzodiazepines, significantly reduced unpunished responding. The 5-HT2A/2C receptor antagonists ritanserin (2 mg/kg), mianserin (8 mg/kg), and mesulergine (0.1 mg/kg) significantly increased the rates of punished responding, whereas 0.5-2 mg/kg ketanserin, that has higher affinity for 5-HT2A than 5-HT2C receptors, had no effect. Antagonists, at 5-HT3 receptors such as ondansetron (0.001-0.1 mg/kg) and tropisetron (0.001-0.1 mg/kg), had no effect on punished or unpunished responding. The results show that agents acting as full or partial agonists at 5-HT1A receptors and blockers of postsynaptic 5-HT2C receptors have anxiolytic-like effects in a model of punished operant responding, whereas antagonists at 5-HT1A and 5-HT3 receptors have no such effect.
Cervo
L
L
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Samanin
R
R
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002707:Chlordiazepoxide / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D011678:Punishment; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D002707:Chlordiazepoxide; D007650:Ketanserin; D003975:Diazepam