Review, Jun/20:Regulation of GABA A Receptor Subunit Expression in Substance Use

The full title of this American review is "Regulation of GABA A Receptor Subunit Expression in Substance Use Disorders ".

https://pubmed.ncbi.nlm.nih.gov/32580510/

Abstract

The modulation of neuronal cell firing is mediated by the release of the neurotransmitter GABA (γ-aminobuytric acid), which binds to two major families of receptors. The ionotropic GABAA receptors (GABAARs) are composed of five distinct subunits that vary in expression by brain region and cell type. The action of GABA on GABAARs is modulated by a variety of clinically and pharmacologically important drugs such as benzodiazepines and alcohol. Exposure to and abuse of these substances disrupts homeostasis and induces plasticity in GABAergic neurotransmission, often via the regulation of receptor expression. Here, we review the regulation of GABAAR subunit expression in adaptive and pathological plasticity, with a focus on substance use. We examine the factors influencing the expression of GABAAR subunit genes including the regulation of the 5' and 3' untranslated regions, variations in DNA methylation, immediate early genes and transcription factors that regulate subunit expression, translational and post-translational modifications, and other forms of receptor regulation beyond expression. Advancing our understanding of the factors regulating GABAAR subunit expression during adaptive plasticity, as well as during substance use and withdrawal will provide insight into the role of GABAergic signaling in substance use disorders, and contribute to the development of novel targeted therapies.

Thanks for posting this.

“Exposure to and abuse of these substances disrupts homeostasis and induces plasticity in GABAergic neurotransmission, often via the regulation of receptor expression. Here, we review the regulation of GABAAR subunit expression in adaptive and pathological plasticity, with a focus on substance use.”

“Advancing our understanding of the factors regulating GABAAR subunit expression during adaptive plasticity, as well as during substance use and withdrawal will provide insight into the role of GABAergic signaling in substance use disorders, and contribute to the development of novel targeted therapies.”

“Regardless of the complexity, changes in GABAAR expression appear to be a consistent hallmark of the maladaptive plasticity that occurs with repeated exposure to substances of abuse as well as withdrawal, warranting further detailed study. Future studies may endeavor to link changes in specific subunits, across multiple brain areas, in association with specific timepoints following exposure. “

4.1 and 4.4 are the benzo and withdrawal sections.

Hi cs123,

You're welcome. I forgot to post the full study in my original post....

It's here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352578/pdf/ijms-21-04445.pdf 

Thank you for this posting. I translated to Japanese. https://benzoinfojapan.org/doctors-article/22

I guess this study shed a light to mitigate withdrawal symptoms, although I am not sure if it's possible to pull/put subunits from GABAA receptors of living human body..