Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Oct 12:1174:47-52.
doi: 10.1016/j.brainres.2007.07.077. Epub 2007 Aug 16.

Effect of chronic administration of ethanol on the regulation of the delta-subunit of GABA(A) receptors in the rat brain

C R Marutha Ravindran  1 , Ashok K Mehta, Maharaj K Ticku
Affiliations

Effect of chronic administration of ethanol on the regulation of the delta-subunit of GABA(A) receptors in the rat brain

C R Marutha Ravindran et al. Brain Res. .

Abstract

In the present study, we investigated the effect of chronic ethanol (CE) administration on the polypeptide levels of the delta-subunit of GABA(A) receptors and [(3)H]muscimol binding to the immunoprecipitated delta-subunit-containing GABA(A) receptor assemblies in the rat brain. CE administration resulted a down-regulation of polypeptide levels of the delta-subunit of GABA(A) receptors in the rat cerebellum and hippocampus, whereas there were no changes in the delta-subunit polypeptide levels in the rat cerebral cortex. Further, CE administration caused a down-regulation of native delta-subunit-containing GABA(A) receptor assemblies in the rat cerebellum as determined by [(3)H]muscimol binding to the immunoprecipitated receptor assemblies. These results indicate that the delta-subunit-containing GABA(A) receptors may play a role in chronic ethanol-induced tolerance and dependence.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Effect of chronic administration of ethanol and its withdrawal on the polypeptide levels of the δ-subunit of GABAA receptors in the rat (A) cerebellum, i.e., CB, (B) hippocampus, i.e., HC, and (C) cerebral cortex, i.e., CC. Panel (a): Western blot for the GABAA receptors δ-subunit polypeptide; panel (b): reprobed with actin; and panel (c): percentage polypeptide levels of the δ-subunit of GABAA receptors. Molecular mass of the δ-subunit of GABAA receptors was found to be 54 kDa in Western blot analysis. Each value is % mean ± S.E.M derived from three different Western blots performed on different days using pooled tissue from 10 rats in each group. % Polypeptide levels were calculated by comparing the intensity of each band with the average control intensity (100%) from three different Western blots as detailed in materials and methods. Lane 1: proteins extracted from control tissues (saline-administered rats); lane 2: proteins extracted from tissues harvested from chronic ethanol-administered rats; lane 3: proteins extracted from tissues harvested from ethanol-withdrawn rats (48 h). *p < 0.01 as compared to the control group by one-way analysis of variance (ANOVA) followed by Dunnett test.
Fig. 1
Fig. 1
Effect of chronic administration of ethanol and its withdrawal on the polypeptide levels of the δ-subunit of GABAA receptors in the rat (A) cerebellum, i.e., CB, (B) hippocampus, i.e., HC, and (C) cerebral cortex, i.e., CC. Panel (a): Western blot for the GABAA receptors δ-subunit polypeptide; panel (b): reprobed with actin; and panel (c): percentage polypeptide levels of the δ-subunit of GABAA receptors. Molecular mass of the δ-subunit of GABAA receptors was found to be 54 kDa in Western blot analysis. Each value is % mean ± S.E.M derived from three different Western blots performed on different days using pooled tissue from 10 rats in each group. % Polypeptide levels were calculated by comparing the intensity of each band with the average control intensity (100%) from three different Western blots as detailed in materials and methods. Lane 1: proteins extracted from control tissues (saline-administered rats); lane 2: proteins extracted from tissues harvested from chronic ethanol-administered rats; lane 3: proteins extracted from tissues harvested from ethanol-withdrawn rats (48 h). *p < 0.01 as compared to the control group by one-way analysis of variance (ANOVA) followed by Dunnett test.
Fig. 1
Fig. 1
Effect of chronic administration of ethanol and its withdrawal on the polypeptide levels of the δ-subunit of GABAA receptors in the rat (A) cerebellum, i.e., CB, (B) hippocampus, i.e., HC, and (C) cerebral cortex, i.e., CC. Panel (a): Western blot for the GABAA receptors δ-subunit polypeptide; panel (b): reprobed with actin; and panel (c): percentage polypeptide levels of the δ-subunit of GABAA receptors. Molecular mass of the δ-subunit of GABAA receptors was found to be 54 kDa in Western blot analysis. Each value is % mean ± S.E.M derived from three different Western blots performed on different days using pooled tissue from 10 rats in each group. % Polypeptide levels were calculated by comparing the intensity of each band with the average control intensity (100%) from three different Western blots as detailed in materials and methods. Lane 1: proteins extracted from control tissues (saline-administered rats); lane 2: proteins extracted from tissues harvested from chronic ethanol-administered rats; lane 3: proteins extracted from tissues harvested from ethanol-withdrawn rats (48 h). *p < 0.01 as compared to the control group by one-way analysis of variance (ANOVA) followed by Dunnett test.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aguayo LG, Peoples RW, Yeh HH, Yevenes GE. GABAA receptors as molecular sites of ethanol action. Direct or indirect actions? Curr. Top. Med. Chem. 2002;2:869–885. - PubMed
    1. Benke D, Mertens S, Trzeciak A, Gillessen D, Mohler H. GABAA receptors display association of γ2-subunit with α1- and β2/3-subunits. J. Biol. Chem. 1991;266:4478–4483. - PubMed
    1. Bjornstrom K, Sjolander A, Schippert A, Eintrei C. A tyrosine kinase regulates propofol-induced modulation of the β-subunit of the GABAA receptor and release of intracellular calcium in cortical rat neurones. Acta Physiol. Scand. 2002;175:227–235. - PubMed
    1. Borghese CM, Storustovu SI, Ebert B, Herd MB, Belelli D, Lambert JJ, Marshall G, Wafford KA, Harris RA. The δ subunit of γ-aminobutyric acid type A receptors does not confer sensitivity to low concentrations of ethanol. J. Pharmacol. Exp. Ther. 2006;316:1360–1368. - PubMed
    1. Cagetti E, Liang J, Spigelman I, Olsen RW. Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol. Pharmacol. 2003;63:53–64. - PubMed

Publication types