Following long-term training with citalopram, both mirtazapine and mianserin block its discriminative stimulus properties in rats

Dekeyne, Anne; Iob, Loretta; Millan, Mark J.
January 2001
Psychopharmacology;2001, Vol. 153 Issue 3, p389
Academic Journal
Abstract Rationale: The discriminative stimulus (DS) properties of the selective serotonin (5-HT) uptake inhibitor (SSRI), citalopram, are mediated by 5-HT[sub 2C] receptors. Interestingly, the "atypical" antidepressants, mianserin and mirtazapine, behave as antagonists' at 5-HT[sub 2C] receptors. Objective: Herein, we evaluated the influence of mianserin and mirtazapine upon the DS effects of citalopram. Methods: In a two-lever drug discrimination procedure, rats initially trained to discriminate citalopram (2.5 mg/kg, J.p.) from saline were retrained with a lower dose of citalopram (0.63 mg/kg, i.p.). Subsequently, generalization and antagonist studies were conducted with mianserin and mirtazapine. Results: Both dose-dependently blocked, but did not generalize to, the DS properties of citalopram without markedly disrupting response rates. Their effective dose[sup 50s] were 0.1 and 1.4 mg/kg, s.c., respectively. Conclusion: These observations are consistent with a role of 5-HT[sub 2C] receptors in mediation of the interoceptive properties of SSRIs and suggest that the DS effects of citalopram are not related to its "antidepressant" properties per se. Finally, they underline the distinctive nature of mirtazapine and mianserin as compared to antidepressant agents which interact with 5-HT uptake sites.


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