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.
Sundstrom-Poromaa
Inger
I
Department of Physiology and Pharmacology, SUNY Downstate Medical Center, 450 Clarkson Ave., Brooklyn, New York 11203, USA.
Smith
Deborah H
DH
Gong
Qi Hua
QH
Sabado
Thomas N
TN
Li
Xinshe
X
Light
Adam
A
Wiedmann
Martin
M
Williams
Keith
K
Smith
Sheryl S
SS
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