We examined the influence of imipramine and lithium on wet-dog shakes induced by the (+/-)-DOI, 5-HT2A receptor agonist in adrenocorticotropic hormone (ACTH)-treated rats. The administration of imipramine for 14 days decreased the (+/-)-DOI-induced wet-dog shakes response; chronic administration of lithium for 14 days, however, had no effect. Chronic ACTH (100 microg/rat sc) treatment increased the wet-dog shake response induced by (+/-)-DOI. This effect of ACTH for 14 days, increasing the (+/-)-DOI-induced wet-dog shakes, was not inhibited by a 14-day administration of imipramine. Chronic coadministration of imipramine and lithium, lasting 14 days, decreased the wet-dog shakes response induced by (+/-)-DOI in rats treated with ACTH for 14 days. These findings indicate that lithium inhibits the hyperfunction of the 5-HT2A receptor in rats treated with ACTH when coadministered with imipramine.