TY - JOUR
T1 - Morphine-induced conditioned place preference and effects of morphine pre-exposure in adolescent and adult male C57BL/6J mice
AU - Koek, Wouter
N1 - Funding Information:
The author thanks Jason Persyn, Chris Limas, Bindumahi Sudaabattula, and Sonia Cano for technical assistance. The work was supported by the US Public Health Service Grant DA23261.
Publisher Copyright:
© 2014, Springer-Verlag Berlin Heidelberg.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Conditioned place preference
KW - Locomotion
KW - Morphine
KW - Mouse
KW - Sensitization
KW - Tolerance
KW - Withdrawal
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U2 - 10.1007/s00213-014-3695-y
DO - 10.1007/s00213-014-3695-y
M3 - Article
C2 - 25066361
AN - SCOPUS:84904769222
VL - 233
SP - 2015
EP - 2024
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 11
ER -