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Discriminative stimulus properties of quipazine: mediation by serotonin2 binding sites

RL Friedman, RJ Barrett and E Sanders-Bush

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.

Volume 228, Issue 3, pp. 628-635, 03/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1984 by the American Society for Pharmacology and Experimental Therapeutics.