Increased DOI-induced wet-dog shakes in adrenocorticotropic hormone-treated rats are not affected by chronic imipramine treatment: Possible involvement of enhanced 5-HT_2A-receptor expression in the frontal cortex

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 [³H]-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.