Adolescent oxycodone self administration alters subsequent oxycodone-induced conditioned place preference and anti-nociceptive effect in C57BL/6J mice in adulthood.
Adolescent and young adult abuse of short-acting MOP-r agonists such as oxycodone is a pressing public health issue. Few preclinical studies have examined how adolescent exposure to oxycodone impacts its effects in the transition to adulthood.



To determine in mice how chronic adolescent oxycodone self-administration (SA) affects subsequent oxycodone-induced conditioned place preference (CPP), locomotor activity, and anti-nociception once mice reach early adulthood.



Adolescent C57BL/6J male mice (4 weeks old, n = 6-11) and adult mice (10 weeks old, n = 6-10) were surgically implanted with indwelling jugular catheters. Mice then acquired oxycodone self-administration (14 consecutive 2-hr daily sessions; 0.25 mg/kg/infusion) followed by a 14-day drug-free (withdrawal) period in home cage. After the 14-day drug-free period, mice underwent a 10-day oxycodone CPP procedure (0, 1, 3, 10 mg/kg i.p.) or were tested for acute oxycodone-induced antinociception in the hot plate assay (3.35, 5, 7.5 mg/kg i.p.).



Mice that self-administered oxycodone during adolescence exhibited greater oxycodone-induced CPP (at the 3 mg/kg dose) than their yoked saline controls and mice that self-administered oxycodone during adulthood. Oxycodone dose-dependently increased locomotor activity, but sensitization developed only to the 3 mg/kg in the mice that underwent oxycodone self-administration as adolescents. Mice that self-administered oxycodone as adolescents decreased in the anti-nociceptive effects of oxycodone in one dose (5 mg/kg), whereas animals that self-administered oxycodone as adults did not show this effect.



Chronic adolescent oxycodone self-administration led to increased oxycodone-induced CPP (primarily 1 and 3 mg/kg, i.p.) and reduced antinociceptive effect of oxycodone (5 mg/kg, i.p.) in adulthood.
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA. Electronic address: zhangyo@rockefeller.edu.
Yong
Y
Zhang
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
Kyle
K
Windisch
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
Joshua
J
Altschuler
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
Sage
S
Rahm
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
Eduardo R
ER
Butelman
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA.
Mary Jeanne
MJ
Kreek
D000700:Analgesics / Q000008:administration & dosage; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059225:Nociception / Q000187:drug effects*; D010098:Oxycodone / Q000008:administration & dosage*; D012646:Self Administration
D000700:Analgesics; D000701:Analgesics, Opioid; D010098:Oxycodone
Adolescent; Conditioned place preference; Hotplate test; Oxycodone; Self administration