Morphine-induced conditioned place preference and effects of morphine pre-exposure in adolescent and adult male C57BL/6J mice

Rationale: Given the increasing abuse of prescription opioids, particularly in adolescents, surprisingly few preclinical studies have explored effects of opioids in adolescents (versus adults). Objectives: This study compared the conditioned rewarding effects of morphine, without (experiment 1) and with morphine pre-exposure (experiment 2), in adolescent and adult male mice. Methods: Experiment 1: On each of three consecutive days, one of the two conditioning sessions was preceded by an injection of a particular dose of morphine (0.1, 0.32, 1, 3.2, 10, 32, or 100 mg/kg, intraperitoneal) and the other by saline; place preference was tested on day 4. Experiment 2: Mice received once daily injections of saline or a particular dose of morphine (17.8 or 56 mg/kg) for 4 days, and 3 days later, place conditioning with morphine (0.32, 1, 3.2, or 10 mg/kg) began. Results: In both experiments, morphine induced conditioned place preference along similar inverted U-shaped dose–response curves in adolescent and adult mice, with maximal effects between 0.32 and 10 mg/kg. Morphine pre-exposure did not sensitize morphine-induced conditioned place preference; instead, tolerance occurred, but only in adults. Adolescents were more sensitive than adults to morphine-induced locomotor stimulation. Response to novelty predicted the locomotor stimulating effects of morphine in adolescents, but not its rewarding effects. Conclusions: The rewarding effects of morphine were similar in adolescent and adult mice but showed differential tolerance after morphine pre-exposure. Adolescents were more sensitive than adults to the acute locomotor stimulating effects of morphine, consistent with dopamine systems involved in locomotor activity being overactive during adolescence.