DISCRIMINATIVE STIMULUS PROPERTIES OF QUIPAZINE - MEDIATION BY SEROTONIN2 BINDING-SITES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 228  (3) , 628-635
Abstract
The relative abilities of putative serotonin (5-HT) antagonists [loxapine, thioridazine, methysergide, metergoline, cinanserin, cyproheptadine, mianserin, desipramine, promethazine and BC-105 (4[1-methyl-piperidylidene-(4)]9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophene)] 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 [median inhibitory concentration] values to 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 = 0.57). No correlation existed between effects on the behavioral measure and affinities for the 5-HT1 site (r = 0.15). The quipazine cue is possibly mediated by an action at central 5-HT2 sites.