A role for mu opioid receptors in cocaine-induced activity, sensitization, and reward in the rat

Rational Considerable evidence suggests that the endogenous opioid system plays a role in mediating the behavioral effects of psychostimulants. Opioidergic drugs have been shown to have profound effects on cocaine-induced behavioral sensitization and conditioned reward. However, the role specifically of the mu opioid receptor in this regard is unclear as most previous pharmacological studies have used nonselective opioid receptor ligands. Objectives The objective of this series of experiments was to elucidate the role of mu opioid receptors in the behavioral effects of cocaine in the rat. Materials and methods Adult male rats were used to assess the effects of the selective mu opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr (CTAP) on acute hyperactivity, locomotor sensitization, and conditioned place preference induced by cocaine. Intracerebroventricular administration of CTAP, 4 g, was paired with peripheral injections of cocaine, 10-15 mg/kg. Results Mu receptor blockade significantly attenuated cocaine-induced hyperactivity, as well as the development of behavioral sensitization. Pretreatment with CTAP also prevented the development of conditioned place preference to cocaine. Administration of CTAP alone had neither effect on locomotor activity nor did it demonstrate aversive or rewarding properties. Conclusions These results suggest that activation of mu opioid receptors by endogenous opioids is an important contributor to cocaine-induced hyperactivity and the development of behavioral sensitization and conditioned reward.