The rewarding action of acute cocaine is reduced in β-endorphin deficient but not in μ opioid receptor knockout mice

We have previously shown that beta-endorphin plays a functional role in the rewarding effect of acute cocaine. Considering that beta-endorphin has high affinity for the mu opioid receptor, we determined the role of this receptor in the rewarding action of acute cocaine. For comparison, we assessed the role of the mu opioid receptor in the rewarding effect of acute morphine. We also examined the effect of intracerebroventricular (i.c.v.) administration of beta-funaltrexamine (beta-FNA), an irreversible mu opioid receptor antagonist, on the rewarding action of acute cocaine as well as that of morphine. Using the conditioned place preference (CPP) paradigm as an animal model of reward, we first assessed the rewarding action of cocaine in mice lacking beta-endorphin or the mu opioid receptor and their respective wild-type littermates/controls. Mice were tested for preconditioning place preference on day 1, conditioned once daily with saline/cocaine (30 mg/kg, i.p.) or cocaine/saline on days 2 and 3, and then tested for postconditioning place preference on day 4. We next studied the rewarding action of acute morphine in mu knockout mice and their wild-type controls. The CPP was induced by single alternate-day saline/morphine (10 mg/kg, s.c.) or morphine/saline conditioning. We finally determined the effect of beta-FNA on CPP induced by cocaine or morphine in wild-type mice, in which mice were treated with saline or beta-FNA (9ug/3 mu l; i.c.v.) a day prior to the preconditioning test day. Our results revealed that morphine induced a robust CPP in wild-type mice but not in mice lacking the mu opioid receptor or in wild-type mice treated with beta-FNA. In contrast, cocaine induced CPP in mu knockout mice as well as in wild-type mice treated with beta-FNA. On the other hand, cocaine failed to induce CPP in mice lacking beta-endorphin. These results illustrate that beta-endorphin is essential for the rewarding action of acute cocaine, but the mu opioid receptor may not mediate the regulatory action of endogenous beta-endorphin. (C) 2012 Elsevier B.V. All rights reserved.