Morphine‐induced motor stimulation and ataxia: age‐related differences in mice

Given evidence for age‐related differences in the effects of drugs of abuse, surprisingly few preclinical studies have explored effects of opioids in adolescents (versus adults). The present study compared the motor stimulating and ataxic effects of morphine in adolescent and adult mice. Morphine (3.2 – 56 mg/kg, i.p.) increased locomotion along an inverted U‐shaped dose‐response curve in adolescent, late adolescent, and adult male C57BL/6J mice. In all age groups, the minimum effective dose to enhance locomotion was 10 mg/kg, and maximal stimulation was observed at 17.8 mg/kg. However, maximal stimulation was higher in adolescents than in adults. In contrast, adolescents showed less ataxia than adults when given morphine (5.6 – 100 mg/kg, i.p.). Morphine pharmacokinetics was similar in all age groups. Morphine levels peaked in plasma at 10 min after i.p. injection and in brain at 45 min. Together, these findings could be taken to indicate that adolescent animals are more sensitive to motor stimulating effects of morphine. However, increased locomotion could also be due to less interference by ataxia. Thus, it is possible that morphine‐induced motor stimulation appears enhanced in adolescents compared with adults not because adolescents are more sensitive to the motor stimulating effects of morphine, but because they are less sensitive to its ataxic effects. Support: DA23261 (WK), DA17918 (CF)