Discriminative stimulus properties of quipazine: mediation by serotonin2 binding sites.
The relative abilities of putative serotonin (5-HT) antagonists to block the quipazine discriminative cue were compared with their relative potencies to compete for the 5-HT1 and 5-HT2 binding sites in the brain. Male Sprague-Dawley rats were trained to discriminate 2.5 mg/kg of quipazine from saline. Once training was complete, antagonists were administered 90 min before a 5-min test with 1 mg/kg of quipazine, a dose which gave 75% responding on the quipazine lever. A dose-response curve was generated for each antagonist and an ID50 value (dose that inhibits responding to 50% on the quipazine lever) was determined by log-logit analysis. The binding of [3H]-5-HT to the 5-HT1 site and of [3H]spiperone to the 5-HT2 site was determined in crude membranes prepared from frontal cortex ( [3H]spiperone) or pons-medulla ( [3H]-5-HT) of naive rats. IC50 values for the antagonists were determined by log-logit analyses of competition binding curves. The ID50 values for the blockade of the quipazine discrimination by the 5-HT antagonists correlated significantly with their affinities for the 5-HT2 binding site (r = 0.87). In contrast, no correlation existed between effects on the behavioral measure and affinities for the 5-HT1 site (r = 0.15). These results suggest that the quipazine cue is mediated by an action at central 5-HT2 sites.
D000818:Animals; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D011814:Quipazine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013134:Spiperone / Q000378:metabolism
D011804:Quinolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D011814:Quipazine; D013134:Spiperone; D008238:Lysergic Acid Diethylamide