The Role of GABA in Alcohol Use Disorders
Alcohol use disorders are a result of heightened pleasure from repeated alcohol drinking behavior. 6 There are genetic components and environmental factors linked to alcohol use disorder. There is genetic heterogeneity in the risk of developing alcohol dependence, with different genetic loci contributing to the risk. 6 The linkage can be narrowed down to either alcohol dehydrogenase gene cluster or GABRB1 gene in different population period. 7 Standard pharmacological treatment consists of naltrexone or benzodiazepine which work by enhancing GABA neurotransmitter effects and reduce the severity of alcohol withdrawal symptoms. GABA is an inhibitory Neurotransmitter made from glutamate and other enzymes which are involved in feeding behavior, stress responses and alcohol seeking behavior. Alcohol binds to GABA B receptors and potentiates GABA activity resulting in the alcohol induced reactions by the body. 4 Stress also results in cortical releasing factor (CRF). Chronic alcohol exposure increases GABA release and CRF production. CRF potentiates release of GABA. 3
An animal study was performed on a well characterized rat model of long-term alcohol consumption with repeated deprivation phases. Repeated Baclofen administration was performed at different doses and the response was recorded. 2
In animal models. chronic alcohol exposure resulted in alterations of GABA plasticity, signifying changes in GABA production with alcohol consumption. 2 Baclofen, a GABA B receptor agonist with potential to be of therapeutic use in alcohol use disorders was also investigated. In laboratory animal studies on rodents, Baclofen demonstrated to suppress alcohol seeking behavior. 4
GABA plays a significant role in development of alcohol use disorder. Treatment of alcohol use disorder with GABA Agnes is very preliminary and has been proven to be effective in only mice models. Further studies must be conducted on humans to evaluate the role of GABA Agnes and the treatment of alcohol use disorders. Many alcohol use disorder treatments are catered around increasing the unpleasant effects of alcohol and decreasing the pleasant effects of. alcohol which is a very simple approach.
- Zamudio, P. A., Gioia, D. A., Lopez, M., Homanics, G. E., & Woodward, J. J. (2021). The escalation in ethanol consumption following chronic intermittent ethanol exposure is blunted in mice expressing ethanol resistant GluN1 or GluN2A NMDA receptor subunits. Psychopharmacology, 238(1), 271–279. https://doi.org/10.1007/s00213-020-05680-z
- Vengeliene V, Takahashi TT, Dravolina OA, et al. Efficacy and side effects of baclofen and the novel GABAB receptor positive allosteric modulator CMPPE in animal models for alcohol and cocaine addiction. Psychopharmacology (Berl). 2018;235(7):1955-1965. doi:10.1007/s00213- 018- 4893-9Purpose/hypothesis: To examine Baclofen as a therapeutic agent in substance use disorders
- Juarez B, Morel C, Ku SM, et al. Midbrain circuit regulation of individual alcohol drinking behaviors in mice [published correction appears in Nat Commun. 2018 Feb 8;9(1):653]. Nat 2017;8(1):2220. Published 2017 Dec 20. doi:10.1038/s41467-017-02365-8
- Farokhnia M, Schwandt ML, Lee MR, et al. Biobehavioral effects of baclofen in anxious alcohol-dependent individuals: a randomized, double-blind, placebo-controlled, laboratory study. Transl Psychiatry. 2017;7(4):e1108. Published 2017 Apr 25. Doi:10.1038/tp.2017.71
- Farokhnia M, Sheskier MB, Lee MR, et al. Neuroendocrine response to GABA-B receptor agonism in alcohol-dependent individuals: Results from a combined outpatient and human laboratory experiment. Neuropharmacology. 2018;137:230-239. Doi:10.1016/j.neuropharm.2018.04.011
- Kranzler, H. R., & Soyka, M. (2018). Diagnosis and Pharmacotherapy of Alcohol Use Disorder: A Review. JAMA, 320(8), 815–824. https://doi.org/10.1001/jama.2018.11406
- Witkiewitz, K., Litten, R. Z., & Leggio, L. (2019). Advances in the science and treatment of alcohol use disorder. Science advances, 5(9), eaax4043. https://doi.org/10.1126/sciadv.aax4043
- Treatment Approaches for Drug Addiction DrugFacts. National Institute on Drug Abuse website. https://www.drugabuse.gov/publications/drugfacts/treatment-approaches- drug- addiction. January 17, 2019 Accessed February 18, 2021.
- Pandya M, Palpagama TH, Turner C, Waldvogel HJ, Faull RL, Kwakowsky A. Sex- and age- related changes in GABA signaling components in the human cortex. Biol Sex Differ. 2019;10(1):5. Published 2019 Jan 14. doi:10.1186/s13293- 018-0214-6