We examined the effect of chronic administration of imipramine and bupropion, monoamine reuptake inhibitors, on the duration of immobility in the forced swim test and serotonin (5-HT) 2A receptor function in the form of 5-HT 2A receptor mRNA levels in rats chronically treated with adrenocorticotropic hormone (ACTH). The immobility-decreasing effect of bupropion without imipramine did not influence the chronic ACTH treatment. The effect on the expression of 5-HT 2A receptor mRNA of chronic ACTH treatment was decreased by bupropion, but not imipramine. These results suggest that bupropion has the effect of reducing immobility time in the forced swim test in the tricyclic antidepressant-resistant depressive model induced by chronic ACTH treatment in rats, and that decreased 5-HT 2A receptor mRNA levels may be involved in this phenomenon.

We examined the influence of 8-hydroxy-2-di-n-propylamino tetralin (8- OH

Abstract. We examined the influence of imipramine, a traditional tricyclic antidepressant, on the binding to serotonin (5-HT) 2 receptors and levels of 5-HT 2A -receptor mRNA in the frontal cortex of rats treated with adrenocorticotropic hormone (ACTH). Chronic treatment with ACTH significantly increased the binding of [3 H]-ketanserin to 5-HT 2 receptors and the expression of 5-HT 2A -receptor mRNA in the frontal cortex. However, it did not alter the concentration of 5-HT or 5-hydroxyindole acetic acid. The effect of chronic ACTH treatment on 5-HT 2 receptor and 5-HT 2A -receptor mRNA levels was not altered by the chronic administration of imipramine. Also, imipramine did not affect the hyperfunction of 5-HT 2A receptors caused by chronic ACTH treatment. These findings suggest that chronic treatment with ACTH acts to increase 5-HT 2A -receptor synthesis through increased gene transcription, without modulating presynaptic serotonergic neurotransmission.