A study of oral morphine preference in inbred mouse strains

C57BL/6J mice, in two-bottle choice paradigms, show increased oral morphine consumption, compared with DBA/2J mice. To determine whether this C57 morphine preference reflects differences in the receptor-mediated, reward-based action of morphine (as opposed to pharmacokinetic or gustatory differences), three experiments were performed. Consistent with previous two-bottle choice experiments, C57 mean (± S.D.) morphine consumption was 18 ± 3 mg/kg/day, while the DBA mice consumed 1.4 ± 1.2 mg/kg/day. Intraperitoneal naltrexone produced a 50% decrease in C57 morphine consumption (p < 0.01), while DBA mice showed no change. Consumption of fluid from the control bottle was not changed for either strain. Fifteen and 30 min after oral consumption of a morphine solution, plasma levels of morphine and its glucuronide derivative were not different between these two strains. C57 mice maintained a daily morphine intake of approximately 20 mg/kg across morphine concentrations of 0.05–0.4 mg/ml. These experiments suggest that the difference in oral morphine preference between C57 and DBA mice represents a reward-based mechanism which is mediated through opiate receptors.