The effect of chronic administration of the tricyclic antidepressant, desipramine, or the monoamine oxidase inhibitor (MAOI), nialamide, on the ability of the TRH analog, MK-771, to induce wet-dog shakes in rats was examined. MK-771 at a dose of 3 mg/kg produced significantly fewer wet-dog shakes in those animals treated repeatedly with either nialamide or DMI in comparison to those animals treated chronically with saline. Acute administration of these antidepressant compounds did not alter the ability of MK-771 to produce wet-dog shakes in rats. The results of these experiments indicate that TRH responsiveness in the CNS is reduced by chronic but not acute antidepressant drug treatment, and suggest that TRH may be involved in antidepressant drug action.