The role of mu opioid receptor subtypes, mu 1 and mu 2, in morphine-conditioned place preference was examined using ddY and mu 1 opioid receptor-deficient CXBK mice. In ddY mice, the mu receptor agonist morphine caused a dose-related preference for the drug-associated place, but the kappa agonist U-50,488H produced a dose-related place aversion. These results demonstrated that the mouse is available for place preference conditioning using opioids. Under this condition, the influence of pretreatment with the selective mu 1 opioid receptor antagonist naloxonazine on morphine-induced place preference was investigated in ddY mice. Although pretreatment with the selective mu 1 antagonist naloxonazine (35 mg/kg, s.c.) did not modify the morphine-induced place preference, pretreatment with the selective mu antagonist beta-funaltrexamine (beta-FNA 10 mg/kg, s.c.) eliminated the appetitive effect of morphine. Furthermore, morphine (1-5 mg/kg, s.c.) produced a dose-related preference for the drug-associated place in CXBK mice. These findings suggest that the morphine-induced conditioned place preference may be mediated by naloxonazine-insensitive sites (mu 2 opioid receptors). In addition, chronic infusion of the dopamine D1 antagonist SCH23390 (1.0 mg/kg/day) during the conditioning sessions eliminated the morphine-induced place preference in CXBK mice. Similarly, morphine combined with naloxonazine failed to produce the place preference in ddY mice chronically treated with SCH23390. The blocking effect of SCH23390 on the morphine-conditioned place preference suggests that mu 2 receptors may regulate the dopaminergic system, especially dopamine D1 receptors, and are also involved in the reinforcing effects of morphine.