A low density of brain IR2-imidazoline receptive sites has previously been linked to depression. In this study we evaluated brain IR2-binding sites in a rat model of depression, olfactory bulbectomy, and determined the effects of chronic imipramine treatment in vivo on these sites. Compared with sham-operated controls, adaptation to olfactory bulbectomy had no effect on either the density (Bmax) or affinity (KD) of [3H]-idazoxan binding to brain IR2 sites. However, 25 days of imipramine treatment (i.p., 20 mg/kg/day) enhanced significantly the density of IR2 binding sites, with no change in affinity in both the model and the control group. These results indicate that the brain IR2-imidazoline receptive sites might be a target for antidepressants.