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Chronic Ethanol Consumption Differentially Alters GABA A Receptor α1 and α4 Subunit Peptide Expression and GABA A Receptor‐Mediated 36 Cl − Uptake in Mesocorticolimbic Regions of Rat Brain
Author(s) -
Papadeas Sophia,
Grobin A. Chistina,
Morrow A. Leslie
Publication year - 2001
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2001.tb02347.x
Subject(s) - ventral tegmental area , nucleus accumbens , gabaa receptor , muscimol , endocrinology , medicine , chemistry , receptor , protein subunit , ethanol , agonist , pharmacology , biology , biochemistry , dopamine , dopaminergic , gene
Background: Gamma‐aminobutyric acid type A (GABA A ) receptors in the brain are modulated by chronic ethanol exposure via the regulation of their function and expression throughout the central nervous system. Recent studies show that chronic ethanol exposure alters subsequent ethanol self‐administration, effects that are believed to be mediated by subcortical regions of the rat brain including the amygdala (AMG), the nucleus accumbens (NAC), and the ventral tegmental area (VTA). Methods: We evaluated GABA A receptor subunit expression using subunit specific (α1 and α4) immunoblotting of small tissue punches from AMG, NAC, and VTA. GABA A receptor‐mediated 36 Cl − uptake was measured in these brain areas after chronic ethanol consumption for 2 weeks. Results: Regional differences in the effect of chronic ethanol on α1 and α4 subunit expression were found. In the AMG, α1 and α4 subunit expressions were significantly decreased by 21.1 ± 5.5% and 22.0 ± 7.1%, respectively. In the NAC, there was a decrease of 28.1 ± 1.3% in α4 subunit expression ( p < 0.0001), but no change in α1 subunit expression was observed. In the VTA, there were no changes in α1 and α4 subunit expressions. Muscimol‐stimulated Cl − uptake was enhanced in the extended AMG, but not the extended NAC of ethanol‐dependent rats. The muscimol concentration response curve was left‐shifted with a 74% decrease ( p < 0.01) in the EC 50 and a 42% increase ( p < 0.05) in the E max in the AMG of ethanol‐dependent rats. Conclusions: These results suggest that chronic ethanol exposure alters GABA A receptor expression in the AMG and NAC. Decreased expression of α4 subunits is associated with increases in GABA A receptor function in the AMG, but not the NAC. These changes may contribute to alcohol drinking behavior and the development of ethanol dependence.