Voluntary Exercise Ameliorates Chronic Ethanol Withdrawal-Induced Adaptations of Opioid Receptor Expression in the Nucleus Accumbens, Dopamine Release, and Ethanol Consumption
Christina A. Nelson,
James N. Brundage,
Benjamin M. Williams,
Jared K. Baldridge,
Alyssa L. Stockard,
Charlton H. Bassett,
Brandon J. Burger,
Bridger T. Gunter,
Andrew J. Payne,
Jordan T. Yorgason,
Scott C. Steffensen,
Kyle B. Bills
Affiliations
Christina A. Nelson
Department of Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, UT 84606, USA
James N. Brundage
Department of Psychology/Neuroscience, Brigham Young University, Provo, UT 84602, USA
Benjamin M. Williams
Department of Psychology/Neuroscience, Brigham Young University, Provo, UT 84602, USA
Jared K. Baldridge
Department of Psychology/Neuroscience, Brigham Young University, Provo, UT 84602, USA
Alyssa L. Stockard
Department of Psychology/Neuroscience, Brigham Young University, Provo, UT 84602, USA
Charlton H. Bassett
Department of Psychology/Neuroscience, Brigham Young University, Provo, UT 84602, USA
Brandon J. Burger
Department of Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, UT 84606, USA
Bridger T. Gunter
Department of Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, UT 84606, USA
Andrew J. Payne
Department of Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, UT 84606, USA
Jordan T. Yorgason
Department of Psychology/Neuroscience, Brigham Young University, Provo, UT 84602, USA
Scott C. Steffensen
Department of Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, UT 84606, USA
Kyle B. Bills
Department of Biomedical Sciences, Noorda College of Osteopathic Medicine, Provo, UT 84606, USA
Exercise has increasingly been recognized as an adjunctive therapy for alcohol-use disorder (AUD), yet our understanding of its underlying neurological mechanisms remains limited. This knowledge gap impedes the development of evidence-based exercise guidelines for AUD treatment. Chronic ethanol (EtOH) exposure has been shown to upregulate and sensitize kappa opioid receptors (KORs) in the nucleus accumbens (NAc), which is innervated by dopamine (DA) neurons in the midbrain ventral tegmental area (VTA), which may contribute to AUD-related behaviors. In this study, we investigated the impact of voluntary exercise in EtOH-dependent mice on EtOH consumption, KOR and delta opioid receptor (DOR) expression in the NAc and VTA, and functional effects on EtOH-induced alterations in DA release in the NAc. Our findings reveal that voluntary exercise reduces EtOH consumption, reduces KOR and enhances DOR expression in the NAc, and modifies EtOH-induced adaptations in DA release, suggesting a competitive interaction between exercise-induced and EtOH-induced alterations in KOR expression. We also found changes to DOR expression in the NAc and VTA with voluntary exercise but no significant changes to DA release. These findings elucidate the complex interplay of AUD-related neurobiological processes, highlighting the potential for exercise as a therapeutic intervention for AUD.
