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Ethanol-Induced Plasticity of GABAA Receptors in the Basolateral Amygdala

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Abstract

Acute and chronic ethanol (EtOH) administration is known to affect function, surface expression, and subunit composition of γ-aminobutyric acid (A) receptors (GABAARs) in different parts of the brain, which is believed to play a major role in alcohol dependence and withdrawal symptoms. The basolateral amygdala (BLA) participates in anxiety-like behaviors including those induced by alcohol withdrawal. In the present study we assessed the changes in cell surface levels of select GABAAR subunits in the BLA of a rat model of alcohol dependence induced by chronic intermittent EtOH (CIE) treatment and long-term (>40 days) withdrawal and investigated the time-course of such changes after a single dose of EtOH (5 g/kg, gavage). We found an early decrease in surface expression of α4 and δ subunits at 1 h following single dose EtOH treatment. At 48 h post-EtOH and after CIE treatment there was an increase in α4 and γ2, while α1, α2, and δ surface expression were decreased. To relate functional changes in GABAARs to changes in their subunit composition we analyzed miniature inhibitory postsynaptic currents (mIPSCs) and the picrotoxin-sensitive tonic current (Itonic) 48 h after EtOH intoxication. The Itonic magnitude and most of the mIPSC kinetic parameters (except faster mIPSC decay) were unchanged at 48 h post-EtOH. At the same time, Itonic potentiation by acute EtOH was greatly reduced, whereas mIPSCs became significantly more sensitive to potentiation by acute EtOH. These results suggest that EtOH intoxication-induced GABAAR plasticity in the BLA might contribute to the diminished sedative/hypnotic and maintained anxiolytic effectiveness of EtOH.

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Acknowledgments

We thank Werner Sieghart (Medical University of Vienna, Austria) for the generous gift of GABAAR subunit antibodies. We also thank Erin Wenzel for help with some Western blots.

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Correspondence to Igor Spigelman.

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Lindemeyer, A.K., Liang, J., Marty, V.N. et al. Ethanol-Induced Plasticity of GABAA Receptors in the Basolateral Amygdala. Neurochem Res 39, 1162–1170 (2014). https://doi.org/10.1007/s11064-014-1297-z

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  • DOI: https://doi.org/10.1007/s11064-014-1297-z

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