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Psychopharmacology (2016) 233:20152024 DOI 10.1007/s00213-014-3695-y
ORIGINAL INVESTIGATION
Morphine-induced conditioned place preference and effects of morphine pre-exposure in adolescent and adult male C57BL/6J mice
Wouter Koek
Received: 21 March 2014 /Accepted: 11 July 2014 /Published online: 29 July 2014 # Springer-Verlag Berlin Heidelberg 2014
AbstractRationale 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 doseresponse 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.
Keywords Morphine . Conditioned place preference . Locomotion . Sensitization . Tolerance . Withdrawal . Adolescent . Adult . Mouse
The increased prescription of opioids to manage chronic pain has been accompanied by a dramatic rise in opioid abuse that now is a major public health concern (Compton and Volkow 2006). Opioid analgesic abuse is particularly problematic for adolescents, because of uncertain implications of exposure to opioids during adolescence for future addiction. The abuse of opioid analgesics, like that of other...