ACUTE AND CHRONIC FLUOXETINE TREATMENT DECREASES THE SENSITIVITY OF RATS TO REWARDING BRAIN-STIMULATION

The effects of fluoxetine on rewarding brain stimulation were determin ed in eight Wistar rats using a rate-independent discrete-trial thresh old measure. Rats were implanted with bipolar, stainless steel electro des either into the ventral tegmental area (VTA) or medial forebrain b undle (MFB). Acute administration of fluoxetine significantly raised t he reward threshold (decreased sensitivity) at doses of 2.5, 5.0, 10.0 , and 20.0 mg/kg, IPI without altering latency of response. There were no significant differences between VTA and MFB groups. To determine t he effects of chronic treatment, daily injections of 5.0 mg/kg fluoxet ine were administered to rats for 21 days. Chronic treatment of fluoxe tine continued to significantly elevate reward thresholds with no evid ence of tolerance. The results of these experiments suggest that fluox etine does not possess abuse potential and that serotonin produces an inhibitory effect on the mesolimbic dopaminergic reward system. Furthe rmore, these results suggest that the antidepressant effects of fluoxe tine are not the direct result of excitation of brain reward systems, at least in the same manner as abused substances, for example, cocaine . (C) 1998 Elsevier Science Inc.