Chronic coadministration of carbamazepine together with imipramine produces antidepressant-like effects in an ACTH-induced animal model of treatment–resistant depression: Involvement of 5-HT2A receptors?

The use of carbamazepine has been reported to be an effective treatment for severe depression. We have already shown that the antidepressant-like effects of tricyclic antidepressants in the rat forced swim test (FST) are blocked by chronic treatment with adrenocorticotropic hormone (ACTH). In the present study, we examined the effect of the chronic administration of carbamazepine on the FST and the wet-dog shakes induced by (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2A receptor agonist, in ACTH-treated rats. Chronic administration of carbamazepine did not affect the duration of immobility in saline-treated and ACTH-treated rats. The reduction of immobility, induced by chronic administration of imipramine, was blocked by treatment with ACTH. When carbamazepine was administered concurrently with imipramine, we observed a significant decrease in immobility in rats treated with ACTH. Chronic ACTH treatment increased the number of the wet-dog shakes induced by DOI. This effect of ACTH was significantly increased by the coadministration of carbamazepine and imipramine. These results suggest that the use of carbamazepine together with tricyclic antidepressants had the effect of reducing immobility time in the FST in a tricyclic antidepressant–treatment–resistant depressive model induced by chronic ACTH treatment.