GABAergic modulation of ethanol-induced motor impairment.
GABAergic modulation of ethanol-induced motor impairment.
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发表时间：
1982-12
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通讯作者：
G. Frye;G. Breese
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作者：
G. Frye;G. Breese
检查了γ-氨基丁酸（GABA）受体活性的直接或间接药理学操作与乙醇在大鼠中的运动不协调作用的关系。乙醇（1.13-3.0 g/kg i.p.）引起空中扶正高度的剂量依赖性增加。通过脑池内注射 GABA 激动剂蝇蕈醇（0.10 微克）、4,5,6,7-四氢异恶唑（5,4-c）吡啶（3-醇）（1.0 微克）和 GABA（1000 微克）选择性地加重这种运动障碍。 GABA 拮抗剂荷包牡丹碱（脑池内注射 1.0 和 5.0 微克）可减轻损伤。因此，直接操纵 GABA 受体活性可调节乙醇引起的运动不协调。此外，间接作用的 GABA 模拟物，如 γ-乙炔 GABA（100 mg/kg 腹腔注射）、氨氧乙酸（50 mg/kg 腹腔注射）、乙醇胺-O-硫酸盐（250 mg/kg 腹腔注射）和 L-2,4-二氨基丁酸（600 mg/kg 腹腔注射）都增强了乙醇处理引起的空中扶正高度的增加。体外乙醇未能改变[3H]蝇蕈醇与大脑皮质膜的结合，这表明乙醇没有直接竞争GABA结合位点或促进GABA与这些位点的结合。此外，在乙醇或γ-炔属GABA引起的运动障碍程度与三个大脑区域的GABA浓度变化之间没有观察到简单的关系。尽管 GABA 能神经元可能参与乙醇诱导的运动协调抑制的机制，但这种相互作用并不涉及乙醇对 GABA 受体的直接激活。
Direct or indirect pharmacological manipulation of gamma-aminobutyric acid (GABA) receptor activity was examined in relation to the motor incoordinating actions of ethanol in the rat. Ethanol (1.13-3.0 g/kg i.p.) caused a dose-dependent increase in the height of aerial righting. This motor impairment was increased selectively by intracisternal injection of the GABA agonists muscimol (0.10 microgram), 4,5,6,7-tetrahydroisoxazole(5,4-c) pyridin(3-ol) (1.0 microgram) and GABA (1000 micrograms). The GABA antagonist, bicuculline (1.0 and 5.0 micrograms intracisternally), reduced impairment. Thus, direct manipulation of GABA receptor activity modulated motor incoordination caused by ethanol. In addition, indirect-acting GABA-mimetics, such as gamma-acetylenic GABA (100 mg/kg i.p.), aminooxyacetic acid (50 mg/kg i.p.), ethanolamine-O-sulfate (250 mg/kg i.p.) and L-2,4-diaminobutyric acid (600 mg/kg i.p.) all potentiated the increase in the height of aerial righting caused by ethanol treatment. Failure of ethanol to modify the binding of [3H]muscimol to cerebral cortical membranes in vitro suggested there was no direct competition for GABA binding sites or facilitation of the binding of GABA to these sites by ethanol. Also, no simple relationship was observed between the degree of motor impairment caused by either ethanol or gamma-acetylenic GABA and changes in GABA concentration in three brain areas. Although GABAergic neurons may be involved in the mechanism underlying ethanol-induced depression of motor coordination, the interaction does not involve a direct activation of GABA receptors by ethanol.