Discriminative-stimulus effects of quipazine and l-5-hydroxytryptophan in relation to serotonin binding sites in the pigeon.
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.
Department of Psychology, University of Michigan, Ann Arbor.
E A
EA
Walker
T
T
Yamamoto
P J
PJ
Hollingsworth
C B
CB
Smith
J H
JH
Woods
D006916:5-Hydroxytryptophan / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D010856:Columbidae; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000378:metabolism; D007650:Ketanserin / Q000378:metabolism; D007700:Kinetics; D008297:Male; D011743:Pyrimidines / Q000378:metabolism; D011814:Quipazine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D014316:Tritium
D007211:Indoles; D011743:Pyrimidines; D014316:Tritium; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D011814:Quipazine; C043077:ipsapirone; D007650:Ketanserin; D006916:5-Hydroxytryptophan