Fluoxetine Pretreatment Reduces Breaking Points on a Progressive Ratio Schedule Reinforced by Intravenous Cocaine Self-administration in the Rat

Fluoxetine, a specific serotonin re-uptake inhibitor, reduced the breaking points reached by rats on a progressive ratio (PR) schedule reinforced by intravenous cocaine (0.6 mg/inj). This effect was dose-dependent. Specifically, fluoxetine (2.5, 5.0, 10.0, and 20.0 mg/kg, IP) significantly decreased breaking points at all but the lowest dose. These data support a role for the serotonergic system in cocaine reinforcement. We argue that facilitating serotonergic activity reduces the rewarding value of cocaine, thus suggesting an aversive role for serotonin in cocaine reinforcement.