Potential Link Between Exercise and N-Methyl-D-Aspartate Glutamate Receptors in Alcohol Use Disorder: Implications for Therapeutic Strategies

Abstract

Susan Sedhom,1 Nikki Hammond,1 Kyriaki Z Thanos,1 Kenneth Blum,2,3 Igor Elman,4 Abdalla Bowirrat,3 Catherine Anne Dennen,5 Panayotis K Thanos1 1Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA; 2Division of Addiction Research & Education, Center for Sports, Exercise & Global Mental Health, Western University Health Sciences, Pomona, CA, USA; 3Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel; 4Department of Psychiatry, Harvard School of Medicine, Cambridge Health Alliance, Cambridge, MA, USA; 5Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, USACorrespondence: Panayotis K Thanos; Kenneth Blum, Email [email protected]; [email protected]: Alcohol use disorder (AUD) is a significant risk factor, accounting for approximately 13% of all deaths in the US. AUD not only destroys families but also causes economic losses due to reduced productivity, absenteeism, and healthcare expenses. Statistics revealing the sustained number of individuals affected by AUD over the years underscore the need for further understanding of the underlying pathophysiology to advance novel therapeutic strategies. Previous research has implicated the limbic brain regions N-methyl-D-aspartate glutamate receptors (NMDAR) in the emotional and behavioral effects of AUD. Given that aerobic exercise can modulate NMDAR activity and sensitivity to alcohol, this review presents a summary of clinical and basic science studies on NMDAR levels induced by alcohol consumption, as well as acute and protracted withdrawal, highlighting the potential role of aerobic exercise as an adjunctive therapy for AUD. Based on our findings, the utility of exercise in the modulation of reward-linked receptors and AUD may be mediated by its effects on NMDA signaling. These data support further consideration of the potential of aerobic exercise as a promising adjunctive therapy for AUD.Keywords: exercise, alcohol use disorder, AUD, NMDA receptors, brain, reward

Keywords

• exercise
• alcohol use disorder
• aud
• nmda receptors
• brain
• reward