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

Susan Sedhom, Nikki Hammond, Kyriaki Z Thanos, Kenneth Blum, Igor Elman, Abdalla Bowirrat, Catherine Anne Dennen, Panayotis K Thanos
Author Information
  1. Susan Sedhom: Behavioral 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.
  2. Nikki Hammond: Behavioral 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.
  3. Kyriaki Z Thanos: Behavioral 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.
  4. Kenneth Blum: Division of Addiction Research & Education, Center for Sports, Exercise & Global Mental Health, Western University Health Sciences, Pomona, CA, USA. ORCID
  5. Igor Elman: Department of Psychiatry, Harvard School of Medicine, Cambridge Health Alliance, Cambridge, MA, USA. ORCID
  6. Abdalla Bowirrat: Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel. ORCID
  7. Catherine Anne Dennen: Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, USA.
  8. Panayotis K Thanos: Behavioral 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.

Abstract

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

References

  1. Neuropsychopharmacology. 2021 Oct;46(11):1927-1936 [PMID: 34035471]
  2. Psychol Addict Behav. 2021 Jun;35(4):444-457 [PMID: 33956473]
  3. Neurochem Res. 2017 Apr;42(4):1230-1239 [PMID: 28078614]
  4. JAMA Netw Open. 2022 Nov 1;5(11):e2239485 [PMID: 36318209]
  5. Sci Rep. 2022 May 12;12(1):7896 [PMID: 35550587]
  6. Transl Res. 2019 May;207:1-18 [PMID: 30731068]
  7. Behav Brain Res. 2010 Dec 20;215(1):77-82 [PMID: 20615434]
  8. J Neural Transm (Vienna). 2019 Apr;126(4):481-516 [PMID: 30569209]
  9. Biomarkers. 2022 Jun;27(4):306-318 [PMID: 35236200]
  10. Neuron. 2017 Dec 20;96(6):1223-1238 [PMID: 29268093]
  11. J Subst Abuse Treat. 2015 May;52:1-9 [PMID: 25641736]
  12. Behav Brain Res. 2013 Feb 15;239:8-14 [PMID: 23103403]
  13. Front Hum Neurosci. 2022 Feb 22;16:757522 [PMID: 35273485]
  14. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3561-6 [PMID: 11248117]
  15. Alcohol Clin Exp Res. 2003 Oct;27(10):1632-9 [PMID: 14574234]
  16. Alcohol Alcohol. 2012 Sep-Oct;47(5):501-8 [PMID: 22791370]
  17. Pharmacol Ther. 2022 Dec;240:108299 [PMID: 36323379]
  18. Neuropharmacology. 2021 Aug 1;193:108631 [PMID: 34058193]
  19. Addict Biol. 2021 Mar;26(2):e12915 [PMID: 32500613]
  20. Ment Health Phys Act. 2020 Oct;19:100360 [PMID: 33020704]
  21. Neuropsychobiology. 2013;68(1):1-14 [PMID: 23774826]
  22. Drug Alcohol Depend. 2017 Aug 1;177:244-248 [PMID: 28622627]
  23. Neuropharmacology. 2019 Oct;157:107681 [PMID: 31251994]
  24. J Pers Med. 2022 Oct 27;12(11): [PMID: 36579510]
  25. Neurotox Res. 2020 Mar;37(3):702-713 [PMID: 32062779]
  26. Evid Based Complement Alternat Med. 2022 Sep 6;2022:1620816 [PMID: 36110196]
  27. Psychopharmacology (Berl). 2018 Dec;235(12):3363-3379 [PMID: 30392132]
  28. Nat Rev Neurol. 2011 May;7(5):284-94 [PMID: 21487421]
  29. Neurochem Res. 2019 Jan;44(1):133-146 [PMID: 30334175]
  30. Respir Physiol Neurobiol. 2018 Oct;256:67-78 [PMID: 28811138]
  31. Alcohol. 2020 Feb;82:63-70 [PMID: 31473305]
  32. Mol Psychiatry. 2022 Aug;27(8):3468-3478 [PMID: 35484243]
  33. Trends Mol Med. 2023 Dec;29(12):1014-1028 [PMID: 37770379]
  34. Drug Alcohol Depend. 2019 Dec 1;205:107628 [PMID: 31683244]
  35. Int Rev Neurobiol. 2019;147:219-267 [PMID: 31607356]
  36. Behav Brain Res. 2020 Feb 17;380:112444 [PMID: 31866463]
  37. Front Behav Neurosci. 2022 Jun 09;16:893835 [PMID: 35755407]
  38. Behav Brain Res. 2020 May 27;386:112599 [PMID: 32184158]
  39. Int J Ment Health Addict. 2023 Jun 6;:1-13 [PMID: 37363762]
  40. BMC Neurosci. 2018 Nov 12;19(1):73 [PMID: 30419823]
  41. Alcohol Clin Exp Res. 2007 Apr;31(4):582-95 [PMID: 17374037]
  42. Alcohol Clin Exp Res. 1999 Feb;23(2):363-70 [PMID: 10069569]
  43. Neuroscience. 2022 Apr 1;487:166-183 [PMID: 35167938]
  44. Drug Alcohol Depend. 2019 Dec 1;205:107622 [PMID: 31760294]
  45. Addiction. 2022 Mar;117(3):804-814 [PMID: 34288186]
  46. Alcohol Clin Exp Res. 2020 Oct;44(10):1965-1976 [PMID: 32862443]
  47. Brain Plast. 2018 Dec 12;4(1):17-52 [PMID: 30564545]
  48. Sci Rep. 2019 Mar 12;9(1):4165 [PMID: 30862816]
  49. Neuropharmacology. 2019 Apr;148:272-283 [PMID: 30659841]
  50. Front Psychol. 2016 Jan 07;6:1890 [PMID: 26779053]
  51. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6510-2 [PMID: 6579537]
  52. Alcohol Clin Exp Res. 2009 Nov;33(11):1924-34 [PMID: 19673743]
  53. J Biol Chem. 2003 Mar 28;278(13):11020-5 [PMID: 12536146]
  54. Front Psychol. 2020 Sep 29;11:561590 [PMID: 33101132]
  55. Front Cell Neurosci. 2019 Oct 04;13:440 [PMID: 31636539]
  56. Front Psychiatry. 2023 Mar 24;14:1116901 [PMID: 37032937]
  57. Psychopharmacology (Berl). 2020 Jul;237(7):1917-1929 [PMID: 32488351]
  58. Br J Sports Med. 2017 Jul;51(14):1058-1064 [PMID: 28087569]
  59. J Pers Med. 2022 Nov 30;12(12): [PMID: 36556197]
  60. Nat Rev Neurosci. 2009 Aug;10(8):561-72 [PMID: 19571793]
  61. Physiol Rev. 2019 Oct 1;99(4):2115-2140 [PMID: 31507244]
  62. J Appl Physiol (1985). 2022 Dec 1;133(6):1368-1380 [PMID: 36269295]
  63. Neuropharmacology. 2020 Feb;163:107863 [PMID: 31778691]
  64. Pharmacol Biochem Behav. 2020 Sep;196:172980 [PMID: 32593790]
  65. Brain Res. 1996 Jan 8;706(1):123-8 [PMID: 8720499]
  66. Sports Med. 2020 Jan;50(1):151-170 [PMID: 31541410]
  67. Am J Physiol Gastrointest Liver Physiol. 2019 Apr 1;316(4):G453-G461 [PMID: 30702902]
  68. Mol Neurobiol. 2018 Apr;55(4):3112-3130 [PMID: 28466271]
  69. Life Sci. 2019 Aug 1;230:84-88 [PMID: 31128137]
  70. Front Endocrinol (Lausanne). 2023 Nov 24;14:1202349 [PMID: 38084331]
  71. Behav Brain Res. 2018 Nov 1;353:176-184 [PMID: 30036547]
  72. Sci Adv. 2019 Sep 25;5(9):eaax4043 [PMID: 31579824]
  73. Front Neurosci. 2022 Feb 02;16:820106 [PMID: 35185459]
  74. Arch Virol. 1987;93(3-4):233-45 [PMID: 3030238]
  75. Front Neurosci. 2018 Mar 28;12:200 [PMID: 29643762]
  76. J Neurochem. 1999 Apr;72(4):1523-8 [PMID: 10098857]
  77. J Affect Disord. 2022 Jul 1;308:577-586 [PMID: 35452756]
  78. Int J Mol Sci. 2022 Nov 29;23(23): [PMID: 36499240]
  79. PLoS One. 2015 Mar 06;10(3):e0118721 [PMID: 25747876]
  80. Elife. 2017 Jun 29;6: [PMID: 28661398]
  81. Neurobiol Learn Mem. 2023 Jan;197:107709 [PMID: 36503101]
  82. Int Rev Neurobiol. 2021;160:223-250 [PMID: 34696874]
  83. Dialogues Clin Neurosci. 2009;11(3):333-48 [PMID: 19877500]
  84. J Neurol Sci. 2020 May 15;412:116763 [PMID: 32305746]
  85. Science. 1982 Jun 25;216(4553):1425-7 [PMID: 7089531]
  86. Biol Psychiatry. 2012 Jun 1;71(11):1015-21 [PMID: 21907974]
  87. Neurochem Res. 2019 Jan;44(1):78-88 [PMID: 29307084]
  88. Front Psychiatry. 2022 Jun 09;13:767506 [PMID: 35757224]
  89. Int J Mol Sci. 2020 Nov 29;21(23): [PMID: 33260365]
  90. Subst Use Misuse. 2019;54(14):2290-2303 [PMID: 31369300]
  91. Curr Neuropharmacol. 2021;19(5):610-628 [PMID: 32744976]
  92. Oxid Med Cell Longev. 2020 Feb 13;2020:4293071 [PMID: 32215173]
  93. Theranostics. 2021 Jan 1;11(5):2247-2262 [PMID: 33500723]
  94. Psychol Med. 2017 Dec;47(16):2811-2822 [PMID: 28552086]
  95. Brain Plast. 2020 Dec 29;6(1):123-136 [PMID: 33680851]
  96. Psychopharmacology (Berl). 2020 Feb;237(2):453-463 [PMID: 31712970]
  97. Genes Brain Behav. 2017 Jan;16(1):139-148 [PMID: 27906494]
  98. Neuropharmacology. 2017 Aug 1;122:85-99 [PMID: 28108359]
  99. Prog Neurobiol. 2018 Dec;171:32-49 [PMID: 30316901]
  100. Brain Res. 2005 Jun 28;1048(1-2):69-79 [PMID: 15919065]
  101. Epilepsy Res. 2019 Dec;158:106224 [PMID: 31698280]
  102. Int J Mol Sci. 2021 Aug 12;22(16): [PMID: 34445376]
  103. Nutr Neurosci. 2021 Jun;24(6):443-458 [PMID: 31331257]
  104. Alcohol Clin Exp Res. 2022 Jan;46(1):114-128 [PMID: 34773282]
  105. Front Behav Neurosci. 2021 Feb 11;14:598570 [PMID: 33643005]
  106. Am J Psychiatry. 2018 Jan 1;175(1):86-90 [PMID: 29301420]
  107. Naunyn Schmiedebergs Arch Pharmacol. 2021 Sep;394(9):1829-1867 [PMID: 33991216]
  108. Genes (Basel). 2019 Sep 17;10(9): [PMID: 31533339]
  109. J Pers Med. 2022 May 25;12(6): [PMID: 35743644]
  110. Prog Neuropsychopharmacol Biol Psychiatry. 2024 Jul 13;133:111008 [PMID: 38641236]
  111. Acta Neurol Scand. 2017 Jan;135(1):4-16 [PMID: 27586815]
  112. Soc Sci Med. 2022 Mar;296:114732 [PMID: 35078103]
  113. Addict Biol. 2019 Nov;24(6):1227-1234 [PMID: 30536923]
  114. J Neurophysiol. 2002 Feb;87(2):705-11 [PMID: 11826039]
  115. Curr Neuropharmacol. 2017;15(4):519-533 [PMID: 27000776]
  116. Clin Mol Hepatol. 2020 Oct;26(4):652-661 [PMID: 33053937]
  117. Neurosci Lett. 2019 Jul 13;705:143-150 [PMID: 31029678]
  118. Front Psychol. 2014 Sep 17;5:919 [PMID: 25278909]
  119. Naunyn Schmiedebergs Arch Pharmacol. 2000 Feb;361(2):206-13 [PMID: 10685878]
  120. Neuropsychopharmacology. 2022 Mar;47(4):840-846 [PMID: 34475522]
  121. Soc Sci Med. 2022 May;301:114887 [PMID: 35316700]
  122. Med Sci Sports Exerc. 2018 Aug;50(8):1596-1602 [PMID: 29613999]
  123. Pharmacol Rev. 2021 Jan;73(1):163-201 [PMID: 33318153]
  124. Eur J Neurosci. 2021 Oct;54(8):6960-6971 [PMID: 32236992]
  125. Appl Physiol Nutr Metab. 2020 Jun;45(6):591-600 [PMID: 31665610]

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