It is estimated that 4.3 million people in the United States abuse prescription opioids (Center for Behavioral Health Statistics and Quality (CBHSQ) 2015) and that these are the second most abused illicit drugs by youths between the ages of 12 and 17. The long-term consequences of adolescent prescription opioid abuse on subsequent drug use in adulthood are unknown. Further, the underlying mechanism(s) associated with these behaviors are not known. Susceptibility of the adolescent brain to environmental insult is due, in part, to the massive neuronal reorganization and growth that occurs during this time. Recent studies have identified epigenetic regulation of several key genes as major contributors to adolescent neuronal development. Using tractable mouse models, we have evidence that adolescent oxycodone exposure augment morphine reward later in adulthood , and this is associated with changes in gene expression in the dopamine reward pathway. We will validate and extend these preliminary findings and identify potential underlying mechanisms by analyzing the epigenetic regulation of target gene expression as well as genome-wide histone post-translational modifications.

Public Health Relevance

Adolescent exposure to the prescription opioid oxycodone significantly enhances morphine reward in adulthood and long-term modifications of the genome (epigenetic) associated with this behavior will be investigated. When completed these experiments will determine if the persistent effects of oxycodone are associated with epigenetic modifications, but we will be in a position to then determine the functional significance of such changes using novel strategies of gene-targeting of epigenetic editing.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DA044017-01A1
Application #
9392342
Study Section
Molecular Neuropharmacology and Signaling Study Section (MNPS)
Program Officer
Pollock, Jonathan D
Project Start
2017-07-01
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Pharmacology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104