A critical role for beta-endorphin in cocaine-seeking behavior.

Endogenous beta-endorphin levels in the brain are elevated in response to cocaine and are downstream of the mesolimbic dopaminergic system. However, beta-endorphin's direct involvement in cocaine reinforcement has not been demonstrated. In the present study, a single bilateral microinjection of anti-beta-endorphin antibodies (4 microg) to the nucleus accumbens during the maintenance phase of cocaine self-administration (1 mg/kg/infusion) significantly increased the number of active and inactive lever responses. The increase in lever responses is reminiscent of rat behavior during extinction of cocaine self-administration. Further, a cocaine dose-response demonstrates that the increased lever presses in anti-beta-endorphin antibody-injected rats was still present after substitution with a lower dose of cocaine. These findings support a critical role for beta-endorphin in the cocaine brain reward system. Copyright 2004 Lippincott Williams & Wilkins