The role of beta-endorphin in the acute motor stimulatory and rewarding actions of cocaine in mice.

RATIONALE: Opioid receptor antagonists have been shown to attenuate the rewarding and addictive effects of cocaine. Furthermore, cocaine has been shown to cause the release of beta-endorphin, an endogenous opioid peptide.

OBJECTIVE: We assessed whether this neuropeptide would play a functional role in cocaine-induced motor stimulation and conditioned place preference (CPP).

MATERIALS AND METHODS: Mice lacking beta-endorphin and their wild-type littermates were habituated to motor activity chambers for 1 h, then injected with cocaine (0, 15, 30, or 60 mg/kg, intraperitoneally) or morphine (0, 5, or 10 mg/kg, subcutaneously), and motor activity was recorded for 1 h. In the CPP paradigm, mice were tested for baseline place preference on day 1. On days 2 and 3, mice received an alternate-day saline/cocaine (15, 30, or 60 mg/kg) or saline/morphine (10 mg/kg) conditioning session and then tested for postconditioning place preference on day 4.

RESULTS: Cocaine-induced motor stimulation and CPP were both reduced in mice lacking beta-endorphin. On the other hand, motor stimulation and CPP induced by morphine were not altered in mutant mice.

CONCLUSION: The present results demonstrate that the endogenous opioid peptide beta-endorphin plays a modulatory role in the motor stimulatory and rewarding actions of acute cocaine.