Involvement of 5-HT_1A activity in the discriminative stimulus effects of imipramine

Pigeons were trained to discriminate the tricyclic antidepressant imipramine (3.0 or 55.6 mg/kg) from saline. The selective 5-HT_1A 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-HT_1A antagonist with affinity for both 5-HT_1A and α₁ 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 α₁-adrenoreceptor antagonist prazosin, suggesting a dual mediation of imipramine through both 5-HT_1A and α₁-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.