Long-lasting effects of adolescent oxycodone exposure on reward-related behavior and gene expression in mice.
Prescription opioid abuse and transition to heroin use are growing problems in the USA. However, the long-term consequences of adolescent prescription opioid abuse on subsequent drug use and affective-like behavior are unknown.



This study aims to determine if adolescent exposure to oxycodone alters the rewarding effects of morphine, anxiety-like behavior, and reward-related gene expression later in adulthood.



Adolescent male C57Bl/6 mice were exposed to oxycodone (3 mg/kg/day) via osmotic minipumps for 28 days. Following a 28-day withdrawal period, mice were tested in morphine-conditioned place preference paradigm (CPP), morphine sensitization, open field, marble burying, and forced swim (FST) tests. To determine if effects were specific to adolescent exposure, adult mice were exposed to oxycodone for 28 days and underwent 28 days of withdrawal prior to the same behavioral testing schedule. Expression of reward-related genes including dopamine receptor 1 (D1) and dopamine transporter (DAT) in the nucleus accumbens (NAc) and ventral tegmental area (VTA) was examined.



Adolescent oxycodone exposure significantly increased (300 %) response to morphine CPP during adulthood and significantly reduced D1 expression (30 %) in the NAc and DAT expression (75 %) in the VTA. Adult oxycodone exposure did not affect subsequent responses to morphine CPP. Oxycodone exposure did not affect the development of morphine sensitization or affective-like behaviors. Corticosterone response to a stressor (FST) was significantly reduced (65 %) in mice exposed to oxycodone during adolescence but not adulthood.



Adolescent oxycodone exposure enhances rewarding effects of morphine in adulthood with no effect on other affective-like behaviors.
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Translational Research Laboratory, 125 South 31st Street, Philadelphia, PA19104, USA.
Victoria
V
Sanchez
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Translational Research Laboratory, 125 South 31st Street, Philadelphia, PA19104, USA.
Marco D
MD
Carpenter
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Translational Research Laboratory, 125 South 31st Street, Philadelphia, PA19104, USA.
Nicole L
NL
Yohn
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Translational Research Laboratory, 125 South 31st Street, Philadelphia, PA19104, USA. blendy@mail.med.upenn.edu.
Julie A
JA
Blendy
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000209:etiology; D001522:Behavior, Animal / Q000187:drug effects; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010098:Oxycodone / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000378:metabolism; D012201:Reward; D017557:Ventral Tegmental Area / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D009294:Narcotics; D011954:Receptors, Dopamine; D009020:Morphine; D010098:Oxycodone
Anxiety; Conditioned place preference; Dopamine; Morphine; Opioid; Oxycodone; Reward