Beta-funaltrexamine affects cocaine self-administration in rats responding on a progressive ratio schedule of reinforcement

Many studies have shown interactions between μ-opiates and the mesolimbic dopamine (DA) system. Mu-opiate receptor antagonists have been reported to either increase or decrease the rate of cocaine self-administration, and the interpretation of these data has been difficult. In an attempt to further characterize and localize the effect of opiate receptor blockade on the reinforcing effects of cocaine, the μ-opiate irreversible antagonist beta-funaltrexamine (βFNA) was administered locally to different regions of the mesocorticolimbic system. Microinjection of βFNA into the ventral tegmental area (VTA) or the nucleus accumbens (NAcc) had no effect on cocaine self-administration under a fixed ratio (FR) schedule of reinforcement. However, blockade of opiate receptors in both brain regions did attenuate responding for cocaine maintained by a progressive ratio (PR) schedule. Administration of βFNA in the dorsal striatum had no effect under either schedule condition. The present findings suggest that endogenous opiate systems within the mesolimbic DA system modulate the reinforcing effects of cocaine; however, this modulation seems to be schedule dependent.