GABAA receptor α1 and β2 subunit null mutant mice:: Behavioral responses to ethanol

被引:79
作者
Blednov, YA
Walker, D
Alva, H
Creech, K
Findlay, G
Harris, RA
机构
[1] Univ Texas, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA
[2] Univ Texas, Neurobiol Sect, Austin, TX 78712 USA
关键词
D O I
10.1124/jpet.103.049478
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Mice lacking either the alpha1 or beta2 subunit of the GABA(A) receptor were tested for ethanol, saccharin, or quinine consumption, ethanol-conditioned place preference, ethanol-conditioned taste aversion, ethanol-simulated motor activity, and handling-induced seizures following chronic consumption of an ethanol liquid diet. The alpha1 null mutants showed decreased ethanol and saccharin consumption, increased aversion to ethanol, and a marked stimulation of motor activity after injection of ethanol. The beta2 null mutants showed decreased consumption of saccharin and quinine, but not ethanol. Surprisingly, neither mutant showed marked changes in handling induced seizures before or after withdrawal of ethanol. The unique effects of deletion of these two GABA(A) receptor subunits on ethanol responses are discussed in terms of the distinct changes in different populations of GABA(A) receptors.
引用
收藏
页码:854 / 863
页数:10
相关论文
共 40 条
[31]   Mice lacking the long splice variant of the γ2 subunit of the GABAA receptor are more sensitive to benzodiazepines [J].
Quinlan, JJ ;
Firestone, LL ;
Homanics, GE .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2000, 66 (02) :371-374
[32]   Distribution of the major γ-iminobutyric acidA receptor subunits in the basal ganglia and associated limbic brain areas of the adult rat [J].
Schwarzer, C ;
Berresneim, U ;
Pirker, S ;
Wieselthaler, A ;
Fuchs, K ;
Sieghart, W ;
Sperk, G .
JOURNAL OF COMPARATIVE NEUROLOGY, 2001, 433 (04) :526-549
[33]  
SMITH BR, 1992, ALCOHOL ALCOHOLISM, V27, P227
[34]  
Snell LD, 1996, J PHARMACOL EXP THER, V279, P128
[35]  
Stevenson A, 1995, MOL PHARMACOL, V48, P965
[36]   Loss of the major GABAA receptor subtype in the brain is not lethal in mice [J].
Sur, C ;
Wafford, KA ;
Reynolds, DS ;
Hadingham, KL ;
Bromidge, F ;
Macaulay, A ;
Collinson, N ;
O'Meara, G ;
Howell, O ;
Newman, R ;
Myers, J ;
Atack, JR ;
Dawson, GR ;
McKernan, RM ;
Whiting, PJ ;
Rosahl, TW .
JOURNAL OF NEUROSCIENCE, 2001, 21 (10) :3409-3418
[37]  
TOMKINS DM, 1994, ALCOHOL ALCOHOLIS S2, V29, P551
[38]   BENZODIAZEPINE RECEPTOR LIGANDS MODULATE ETHANOL DRINKING IN ALCOHOL-PREFERRING RATS [J].
WEGELIUS, K ;
HONKANEN, A ;
KORPI, ER .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1994, 263 (1-2) :141-147
[39]   Behavioural changes produced by transgenic overexpression of γ2L and γ2S subunits of the GABAA receptor [J].
Wick, MJ ;
Radcliffe, RA ;
Bowers, BJ ;
Mascia, MP ;
Lüscher, B ;
Harris, RA ;
Wehner, JM .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2000, 12 (07) :2634-2638
[40]   Key amino acids in the gamma subunit of the gamma-aminobutyric acid(A) receptor that determine ligand binding and modulation at the benzodiazepine site [J].
Wingrove, PB ;
Thompson, SA ;
Wafford, KA ;
Whiting, PJ .
MOLECULAR PHARMACOLOGY, 1997, 52 (05) :874-881