Hormonally regulated alpha(4)beta(2)delta GABA(A) receptors are a target for alcohol

Nat Neurosci. 2002 Aug;5(8):721-2. doi: 10.1038/nn888.

Abstract

Here we report that low concentrations of alcohol (1-3 mM) increased Cl(-) currents gated by a recombinant GABA(A) receptor, alpha(4)beta(2)delta, by 40-50% in Xenopus laevis oocytes. We also found greater hippocampal expression of receptors containing alpha(4) and delta subunits, using a rat model of premenstrual syndrome (PMS) in which 1-3 mM alcohol preferentially enhanced GABA-gated currents, and low doses of alcohol attenuated anxiety and behavioral reactivity. The alcohol sensitivity of delta-containing receptors may underlie the reinforcing effects of alcohol during PMS, when eye saccade responses to low doses of alcohol are increased.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chlorides / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Ethanol / pharmacology*
  • Female
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Ion Channel Gating / drug effects*
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Patch-Clamp Techniques
  • Premenstrual Syndrome / chemically induced
  • Premenstrual Syndrome / metabolism
  • Progesterone / pharmacology*
  • Protein Subunits
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism*
  • Recombinant Proteins / drug effects
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transfection
  • Xenopus laevis
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Chlorides
  • Protein Subunits
  • RNA, Messenger
  • Receptors, GABA-A
  • Recombinant Proteins
  • Ethanol
  • Progesterone
  • gamma-Aminobutyric Acid