Involvement of opioid mu 1 receptors in morphine-induced conditioned place preference in rats

The main purpose of this study was to evaluate the role of mu 1-opioid receptors in morphine reward. Therefore, we studied the ability of a mu 1-selective antagonist, naloxonazine [15 mg/kg intraperitoneally (IP)], to antagonize the conditioned place preference (CPP) induced by morphine [3 mg/kg subcutaneously (SC)]. In addition, effects of naloxonazine on morphine-induced catalepsy (15 mg/kg), analgesia (3 mg/kg), and hyperthermia (3 mg/kg) were studied. For comparison, the effects of a nonselective opioid receptor antagonist, naltrexone (2.5 mg/kg SC), and a selective delta-opioid receptor antagonist, naltrindole (2 mg/kg IP), on CPP induced by morphine were investigated. Morphine-induced CPP was clearly antagonized by pretreatment with naloxonazine and naltrexone (12 h and 20 min prior to morphine, respectively) but not by naltrindole (15 min before morphine). Naloxonazine also antagonized morphine-induced catalepsy and analgesia but not morphine-induced hyperthermia. Naltrindole did not modify morphine-induced catalepsy. These results suggest an active role for mu 1-opioid receptors in morphine reward, whereas morphine-induced hyperthermia does not appear to be mediated by mu 1-opioid receptors. Furthermore, delta-opioid receptors seem to be without significance in morphine-induced reward.