Extended access oxycodone self-administration and neurotransmitter receptor gene expression in the dorsal striatum of adult C57BL/6 J mice

Abstract

Although non-medical use of oxycodone continues to be a growing problem in the United States, there are no animal studies examining the effects of long-term oxycodone self-administration (SA). The current study was designed to examine chronic oxycodone SA by mice (14days), in novel extended (4h) SA sessions and its effect on selective striatal neurotransmitter receptor mRNA expression. Adult male C57/BL6J mice were either allowed to self-administer oxycodone (0.25mg/kg/infusion, FR1) or served as yoked-saline controls in an extended access paradigm. Mice self-administered oxycodone for 4h/day for 14 consecutive days. Comparison groups with 14-days exposure to 1-h SA sessions were also studied. Within 1h of the last extended SA session, mice were sacrificed, dorsal striatum was isolated and selective neurotransmitter receptor mRNA levels were examined. The oxycodone groups poked the active hole significantly more times than the yoked controls. The number of nose pokes at the active hole rose over the 14days in the oxycodone group with extended access. The expression of 13 neurotransmitter receptor mRNAs was significantly altered in the dorsal striatum, including the gamma-aminobutyric acid (GABA) A receptor beta 2 subunit (Gabrb2) showing experiment-wise significant decrease, as a result of extended oxycodone SA. C57BL/6J mice escalated the amount of oxycodone self-administered across 14 consecutive daily extended sessions, but not 1-h sessions. Decreases in Gabrb2 mRNA levels may underlie escalation of oxycodone intake in the extended access SA sessions.