Hormonally regulated alpha(4)beta(2)delta GABA(A) receptors are a target for alcohol.
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.
Department of Physiology and Pharmacology, SUNY Downstate Medical Center, 450 Clarkson Ave., Brooklyn, New York 11203, USA.
Inger
I
Sundstrom-Poromaa
Deborah H
DH
Smith
Qi Hua
QH
Gong
Thomas N
TN
Sabado
Xinshe
X
Li
Adam
A
Light
Martin
M
Wiedmann
Keith
K
Williams
Sheryl S
SS
Smith
D000818:Animals; D002712:Chlorides / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011293:Premenstrual Syndrome / Q000139:chemically induced / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D021122:Protein Subunits; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002712:Chlorides; D021122:Protein Subunits; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D000431:Ethanol; D011374:Progesterone; D005680:gamma-Aminobutyric Acid