Correlations between subunits of GABAA and NMDA receptors after chronic alcohol treatment or withdrawal, and the effect of taurine in the hippocampus of rats

Alcohol. 2020 Feb:82:63-70. doi: 10.1016/j.alcohol.2019.08.005. Epub 2019 Aug 29.

Abstract

Chronic use of alcohol and its withdrawal impairs the delicate balance between GABAergic and glutamatergic systems. This imbalance includes changes in GABA receptors - importantly in GABAA subtypes - and glutamate receptors, especially in NMDA subtypes. A better comprehension of the different roles of GABAAR and NMDAR subunits could be helpful to define new strategies to counteract the deleterious effects observed during alcohol withdrawal. Taurine, a sulfonated amino acid, has been proposed to attenuate alcohol withdrawal symptoms due to its neuromodulatory properties. In this study, we evaluated the correlations between GABAAR and NMDAR subunits in the hippocampus of rats chronically treated with alcohol or in alcohol withdrawal, and the effects of taurine treatment on these parameters. Male Wistar rats received alcohol (2 g/kg) or water by oral gavage (control), 2 × /day, for 28 days. From day 29 to day 33, withdrawal rats received water instead of alcohol and all groups were reallocated to receive 100 mg/kg taurine or saline intraperitoneally (i.p.), once a day. On day 34, rats were euthanized and the hippocampus was dissected for GABAAR α1, α4, δ, and γ2 and NMDAR GluN2A and GluN2B subunits mRNA expression determination by RT qPCR. There were no differences between groups in the studied GABAAR and NMDA subunits. However, we observed a correlation of α1 and γ2 subunits induced by taurine, while in the alcohol group there was a correlation between α4 and GluN2A. In the group treated with alcohol and taurine, we observed an extra correlation, between α1 and GluN2A. After 5 days of withdrawal, a correlation observed in the control group, between δ and GluN2A, was reestablished. The correlation found between subunits suggests a neuroadaptation of GABAergic and glutamatergic systems in withdrawal rats. Results from this study contribute to the elucidation of the mechanisms beyond neuroadaptations observed in alcohol use and withdrawal.

Keywords: Abstinence; Drug dependence; Ethanol; Glutamate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholism / drug therapy*
  • Alcoholism / metabolism
  • Alcoholism / physiopathology
  • Animals
  • Disease Models, Animal
  • GABAergic Neurons / drug effects*
  • GABAergic Neurons / metabolism
  • Gene Expression Regulation
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Male
  • Neuronal Plasticity / drug effects*
  • Rats, Wistar
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / metabolism
  • Substance Withdrawal Syndrome / physiopathology
  • Taurine / pharmacology*

Substances

  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate
  • Taurine