Discriminative-stimulus effects of quipazine and l-5-hydroxytryptophan in relation to serotonin binding sites in the pigeon

Abstract

The 5-hydroxytryptamine (serotonin; 5-HT) agonists, RU-24969 [5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H-indole, succinate], ipsapirone [2-(4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl)-1,2- benzisothiazol-3-(2H)one-1,1-dioxidehydrochloride], 8-hydroxy-N,N-dipropyl-2-aminotetralin, lysergic acid diethylamide, fenfluramine and N,N-dimethyltryptamine were studied in pigeons trained to discriminate quipazine (1.0 mg/kg) from saline and in pigeons trained to discriminate I-5-HTP (18.0 mg/kg) from saline. Lysergic acid diethylamide, quipazine and fenfluramine generalized to the training stimulus in both groups of pigeons. N,N-dimethyltryptamine generalized to quipazine in all pigeons tested whereas N,N-dimethyltryptamine generalized to I-5-HTP in most pigeons tested. The natural substrate 5-HT and agonists with affinities for the 5-HT1 receptor and its subtypes (8-hydroxy-N,N-dipropyl-2-aminotetralin, ipsapirone, and RU-24969) only generalized in the I-5-HTP-trained pigeons. Equilibrium binding experiments using the ligands [3H]-5-HT and [3H]ketanserin were performed with six areas of pigeon brain and six homologous areas of rat brain. Two populations of 5-HT binding sites were found in brains of both species; one defined by high-affinity binding of [3H]-5-HT and the other defined by high-affinity binding of [3H]ketanserin. Kd values were similar for the two ligands in brains of both species. 5-HT, RU-24969 and ipsapirone displaced [3H]-5-HT but not [3H]ketanserin from pigeon brain membranes. The present study suggests that, in the pigeon, the 5-HT2 receptor might mediate the discriminative-stimulus effects of quipazine, whereas the 5-HT1 receptor might mediate the effects of I-5-HTP.