GABAA-benzodiazepine receptors in the striatum are involved in the sedation produced by a moderate, but not an intoxicating ethanol dose in out-bred Wistar rats

被引:14
作者
June, HL
Cason, CR
Cheatham, G
Lui, RY
Gan, T
Cook, JM
机构
[1] Indiana Univ Purdue Univ, Dept Psychol, Purdue Sch Sci, Indianapolis, IN 46202 USA
[2] Univ Wisconsin, Dept Chem, Milwaukee, WI 53201 USA
关键词
GABA(A)-BDZ receptor; EtOH sedation; striatum; locomotor activity; benzodiazepine inverse agonist; Xenopus oocyte; GABA(A) subunit;
D O I
10.1016/S0006-8993(98)00222-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The role of the dorsal striatum in mediating the sedation produced by a moderate (0.75 g/kg) and an intoxicating (1.25 g/kg) EtOH dose was investigated in the open field by determining the capacity of direct intrastriatal injections of RY 008, a partial inverse agonist of the benzodiazepine (BDZ) receptor, to antagonize EtOH's effects. SR 95531, the competitive high-affinity GABA(A) antagonist was used as a reference compound. Intrastriatal RY 008 (50, 500 ng) and SR 95531 (50 ng) antagonized the sedation produced by the 0.75 g/kg EtOH dose. However, RY 008 did not alter the sedation produced by the 1.25 g/kg dose. RY 008 alone was without effect. RY 008 also failed to negatively modulate GABAergic function at alpha 1 beta 2 gamma 2 or alpha 6 beta 2 gamma 2 receptor subtypes expressed in Xenopus oocytes. Intrastriatal modulation of the moderate EtOH dose was site specific: no antagonism by RY 008 after intraaccumbens infusions was observed. The results suggest that central GABA(A)-BDZ receptors in the dorsal striatum play an important role in mediating the sedation produced by a moderate EtOH dose in the open field. (C) 1998 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:103 / 118
页数:16
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