Abstract
Though interoceptive properties of antidepressants have been described, discriminative stimulus (DS) properties of mirtazapine, which does not affect monoamine reuptake, remain uncharacterized. The objectives of the study are to train rats to recognize a mirtazapine DS, then perform substitution studies with other antidepressants and drugs acting at sites occupied by mirtazapine. Using a two-lever, fixed-ratio 10 schedule, rats were trained to discriminate mirtazapine (2.5 mg/kg, i.p.) from saline. Sessions, 63 +/- 8, were necessary to reach the criterion for 14 rats that all subsequently recognized (100%) mirtazapine at the training dose. Mirtazapine blocks serotonin (5-HT)(2C) receptors, and the 5-HT(2C) antagonists, SB242,084, SB243,213 and S32006, revealed dose-dependent and full (> or =80%) substitution at doses of 2.5, 2.5, and 0.63 mg/kg, respectively. By contrast, the 5-HT(2A) antagonists, MDL100,907 and SR46349-B, the 5-HT(2B) antagonist, SB204,741, and the 5-HT(3) antagonist, ondansetron, showed no significant substitution. Though mirtazapine indirectly recruits 5-HT(1A) receptors, the 5-HT(1A) agonists, buspirone and 8-OH-DPAT, did not substitute. Mirtazapine blocks alpha(2)-adrenoceptors, but several alpha(2)-adreno...Continue Reading
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