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Reduced motor cortex GABA B R function following chronic alcohol exposure.

Reduced motor cortex GABA B R function following chronic alcohol exposure.

Authors :
Peng SY
Shi Z
Zhou DS
Wang XY
Li XX
Liu XL
Wang WD
Lin GN
Pan BX
Voon V
Grace AA
Heilig M
Wong ML
Yuan TF
Source :
Molecular psychiatry [Mol Psychiatry] 2021 Feb; Vol. 26 (2), pp. 383-395. Date of Electronic Publication: 2021 Jan 11.
Publication Year :
2021

Abstract

The GABA <subscript>B</subscript> receptor (GABA <subscript>B</subscript> R) agonist baclofen has been used to treat alcohol and several other substance use disorders (AUD/SUD), yet its underlying neural mechanism remains unclear. The present study aimed to investigate cortical GABA <subscript>B</subscript> R dynamics following chronic alcohol exposure. Ex vivo brain slice recordings from mice chronically exposed to alcohol revealed a reduction in GABA <subscript>B</subscript> R-mediated currents, as well as a decrease of GABA <subscript>B1/2</subscript> R and G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) activities in the motor cortex. Moreover, our data indicated that these alterations could be attributed to dephosphorylation at the site of serine 783 (ser-783) in GABA <subscript>B2</subscript> subunit, which regulates the surface expression of GABA <subscript>B</subscript> R. Furthermore, a human study using paired-pulse-transcranial magnetic stimulation (TMS) analysis further demonstrated a reduced cortical inhibition mediated by GABA <subscript>B</subscript> R in patients with AUD. Our findings provide the first evidence that chronic alcohol exposure is associated with significantly impaired cortical GABA <subscript>B</subscript> R function. The ability to promote GABA <subscript>B</subscript> R signaling may account for the therapeutic efficacy of baclofen in AUD.

Details

Language :
English
ISSN :
1476-5578
Volume :
26
Issue :
2
Database :
MEDLINE
Journal :
Molecular psychiatry
Publication Type :
Academic Journal
Accession number :
33432190
Full Text :
https://doi.org/10.1038/s41380-020-01009-6