Journal of Alcoholism & Drug Dependence
Open Access

Abstract

Self-Administration of Oxycodone by Adolescent and Adult Mice Differentially Affects Hypothalamic Mitochondrial Metabolism Gene Expression

Yong Zhang, Molly Deutsch-Feldman, Michele Buonora, Adam J Brownstein, Keiichi Niikura, Ann Ho, Jurg Ott and Mary Jeanne Kreek

Objective: Illicit prescription drug use among adolescents is a pressing public health concern: 12% of high school students report using prescription opioids with many progressing to use heroin. However, little is known about the effects of these drugs on the adolescent brain compared to the adult brain. This study examined the effect of adolescent oxycodone self-administration on gene expression specifically related to mitochondrial energy metabolism in the hypothalamus as the hypothalamus is involved in the regulation of feeding, reproduction and stress-induced drug seeking behavior.

Methods: Adolescent and adult mice self-administered oxycodone (0.25mg/kg/infusion) or served as yoked saline controls 2 hours daily for 14 days. The hypothalamic mRNAs were analyzed with qPCR using a commercially available “mitochondrial energy metabolism” PCR array containing 84 genes.

Results: mRNA levels of the ubiquinol-cytochrome c reductase, complex III subunit VII (Uqcrq) gene showed an experiment-wise significant increase in adolescents that self-administered oxycodone compared with controls. This effect was not found in adult mice. We also found that mRNA levels of the oxidase assembly 1-like (Oxa1l) gene showed a point-wise significant decrease in adult mice that had self-administered oxycodone. Additionally, twentyseven genes had increased expression in adolescents that self-administered oxycodone. Conversely, adults that self-administered oxycodone had eight genes with lower expression; none showed higher expression.

Conclusion: These findings demonstrate that prescription opioid use caused significant changes of gene expression related to mitochondrial metabolism. The differences between adolescents and adults demonstrate the importance of studying adolescents in order to develop effective treatments.