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Repeated blast model of mild traumatic brain injury alters oxycodone self-administration and drug seeking. Eur J Neurosci 2019 08;50(3):2101-2112

Date

11/21/2018

Pubmed ID

30456793

Pubmed Central ID

PMC6814147

DOI

10.1111/ejn.14281

Scopus ID

2-s2.0-85058419226   3 Citations

Abstract

Each year, traumatic brain injuries (TBI) affect millions worldwide. Mild TBIs (mTBI) are the most prevalent and can lead to a range of neurobehavioral problems, including substance abuse. A single blast exposure, inducing mTBI alters the medial prefrontal cortex, an area implicated in addiction, for at least 30 days post injury in rats. Repeated blast exposures result in greater physiological and behavioral dysfunction than single exposure; however, the impact of repeated mTBI on addiction is unknown. In this study, the effect of mTBI on various stages of oxycodone use was examined. Male Sprague Dawley rats were exposed to a blast model of mTBI once per day for 3 days. Rats were trained to self-administer oxycodone during short (2 h) and long (6 h) access sessions. Following abstinence, rats underwent extinction and two cued reinstatement sessions. Sham and rbTBI rats had similar oxycodone intake, extinction responding and cued reinstatement of drug seeking. A second group of rats were trained to self-administer oxycodone with varying reinforcement schedules (fixed ratio (FR)-2 and FR-4). Under an FR-2 schedule, rbTBI-exposed rats earned fewer reinforcers than sham-exposed rats. During 10 extinction sessions, the rbTBI-exposed rats exhibited significantly more seeking for oxycodone than the sham-injured rats. There was a positive correlation between total oxycodone intake and day 1 extinction drug seeking in sham, but not in rbTBI-exposed rats. Together, this suggests that rbTBI-exposed rats are more sensitive to oxycodone-associated cues during reinstatement than sham-exposed rats and that rbTBI may disrupt the relationship between oxycodone intake and seeking.

Author List

Nawarawong NN, Slaker M, Muelbl M, Shah AS, Chiariello R, Nelson LD, Budde MD, Stemper BD, Olsen CM

Authors

Matthew Budde PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin
Lindsay D. Nelson PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin
Christopher M. Olsen PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Brian Stemper PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Brain Injuries, Traumatic
Cocaine
Drug-Seeking Behavior
Extinction, Psychological
Male
Oxycodone
Rats, Sprague-Dawley
Reinforcement Schedule
Self Administration
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a