Break-points on a progressive ratio schedule reinforced by intravenous cocaine increase following depletion of forebrain serotonin.

The effect of intracerebral injections of 5,7-dihydroxy-tryptamine (5,7-DHT) on cocaine self-administration behavior was assessed. Rats were tested on a progressive ratio (PR) schedule for cocaine reinforcement. The first response on the lever each day produced an IV infusion of cocaine (0.6 mg/injection) after which the requirements of the schedule escalated with each reinforcement until the behavior extinguished. The final ratio completed was defined as the breaking point. Bilateral injections of 5,7-DHT into either the medial forebrain bundle (MFB) or amygdala (AMY) significantly increased the breaking points on the PR schedule compared to vehicle-injected control animals. We interpret these data to indicate that depletion of forebrain serotonin increases the incentive value of cocaine.