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.
OBJECTIVE: 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.
METHODS: 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.).
RESULTS: 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.
CONCLUSION: 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.