Involvement of 5-HT1A activity in the discriminative stimulus effects of imipramine.
Pigeons were trained to discriminate the tricyclic antidepressant imipramine (3.0 or 5.6 mg/kg) from saline. The selective 5-HT1A agonist 8-OH-DPAT (0.03-1.0 mg/kg) resulted in dose-dependent increases in responding on the key correlated with imipramine administration. Doses of 8-OH-DPAT from 0.3 to 1.0 mg/kg substituted completely for imipramine. NAN-190 (0.3-3.0 mg/kg), a putative 5-HT1A antagonist with affinity for both 5-HT1A and alpha 1 receptors, blocked the discriminative stimulus effects of imipramine and resulted in saline-key responding. The discriminative stimulus effects of imipramine were also blocked by administration of the alpha 1-adrenoceptor antagonist prazosin, suggesting a dual mediation of imipramine through both 5-HT1A and alpha 1-adrenoreceptor systems. Although antidepressants have not been used frequently as stimuli in drug discrimination studies, it may be possible to arrive at a more complete understanding of their neurochemical and behavioral effects using this procedure.
Barrett
J E
JE
Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Zhang
L
L
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D010856:Columbidae; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007099:Imipramine; D011224:Prazosin