GABAA Receptor Subtype Mechanisms and the Abuse-Related Effects of Ethanol: Genetic and Pharmacological Evidence

  • Cassie M. Chandler
  • John S. Overton
  • Daniela Rüedi-Bettschen
  • Donna M. PlattEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 248)


Ethanol’s reinforcing and subjective effects, as well as its ability to induce relapse, are powerful factors contributing to its widespread use and abuse. A significant mediator of these behavioral effects is the GABAA receptor system. GABAA receptors are the target for γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS. Structurally, they are pentameric, transmembrane chloride ion channels comprised of subunits from at least eight different families of distinct proteins. The contribution of different GABAA subunits to ethanol’s diverse abuse-related effects is not clear and remains an area of research focus. This chapter details the clinical and preclinical findings supporting roles for different α, β, γ, and δ subunit-containing GABAA receptors in ethanol’s reinforcing, subjective/discriminative stimulus, and relapse-inducing effects. The reinforcing properties of ethanol have been studied the most systematically, and convergent preclinical evidence suggests a key role for the α5 subunit in those effects. Regarding ethanol’s subjective/discriminative stimulus effects, clinical and genetic findings support a primary role for the α2 subunit, whereas preclinical evidence implicates the α5 subunit. At present, too few studies investigating ethanol relapse exist to make any solid conclusions regarding the role of specific GABAA subunits in this abuse-related effect.


Alcohol deprivation effect Drug discrimination GABAA Reinforcing effects Reinstatement Relapse Self-administration Subjective effects Two-bottle choice 



The writing of this chapter was supported by NIH AA016179.


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Cassie M. Chandler
    • 1
  • John S. Overton
    • 2
  • Daniela Rüedi-Bettschen
    • 2
  • Donna M. Platt
    • 1
    • 2
    Email author
  1. 1.Graduate Program in NeuroscienceUniversity of Mississippi Medical CenterJacksonUSA
  2. 2.Department of Psychiatry and Human BehaviorUniversity of Mississippi Medical CenterJacksonUSA

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