Citation

Nawarawong NN, Slaker M, Muelbl M, Shah AS, Chiariello R, Nelson LD, Budde MD, Stemper BD, Olsen CM. Eur. J. Neurosci. 2018; ePub(ePub): ePub.

Affiliation

Neuroscience Research Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA.

Copyright

(Copyright © 2018, Federation of European Neuroscience Societies, Publisher John Wiley and Sons)

DOI

10.1111/ejn.14281

PMID

30456793

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 three days. Rats were trained to self-administer oxycodone during short (2 hour) and long (6 hour) 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 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. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Language: en

Keywords

drug seeking; extinction; male Sprague-Dawley rats; mild traumatic brain injury; opioid self-administration