Extrasynaptic delta-containing GABAA receptors in the nucleus accumbens dorsomedial shell contribute to alcohol intake

Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4459-64. doi: 10.1073/pnas.1016156108. Epub 2011 Feb 22.

Abstract

Recent findings suggest that extrasynaptic δ-subunit-containing GABA(A) receptors are sensitive to low-to-moderate concentrations of alcohol, raising the possibility that these receptors mediate the reinforcing effects of alcohol after consumption of one or a few drinks. We used the technique of viral-mediated RNAi to reduce expression of the GABA(A) receptor δ-subunit in adult rats in localized regions of the nucleus accumbens (NAc) to test the hypothesis that δ-subunit-containing GABA(A) receptors in the NAc are necessary for oral alcohol consumption. We found that knockdown of the δ-subunit in the medial shell region of the NAc, but not in the ventral or lateral shell or in the core, reduced alcohol intake. In contrast, δ-subunit knockdown in the medial shell did not affect intake of a 2% sucrose solution, suggesting that the effects of GABA(A) receptor δ-subunit reduction are specific to alcohol. These results provide strong evidence that extrasynaptic δ-subunit-containing GABA(A) receptors in the medial shell of the NAc are critical for the reinforcing effects of oral ethanol.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Administration, Oral
  • Alcohol Drinking / metabolism*
  • Animals
  • Gene Knockdown Techniques
  • Male
  • Mediodorsal Thalamic Nucleus / metabolism*
  • Mediodorsal Thalamic Nucleus / pathology
  • Nucleus Accumbens / metabolism*
  • Nucleus Accumbens / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Long-Evans
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • Reproducibility of Results
  • Sucrose / metabolism
  • Synapses / metabolism*

Substances

  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, GABA-A
  • Sucrose