Effects of acute and long term clonidine treatment on motor and exploratory activities in rats were investigated in the presence and absence of imipramine. Rats received saline (control), clonidine HCl (0.8 mg/kg), imipramine HCl (30 mg/kg) and clonidine in combination with imipramine for 15 days. Clonidine caused hypoactivity and loss of interest and investment in the environment both acutely (on day 1) and chronically (on day 15). These effects of clonidine were reversed by acute and chronic imipramine pretreatments. Chronic clonidine treatment seemed more suitable in producing a model for depression in rats.