Shelton K.L., Balster R.L.
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
Behav Pharmacol. 1994 Aug;5(4 And 5):441-451.
Both enhancement of GABAergic neurotransmission and antagonism of glutamatergic neurotransmission involving the NMDA receptor have been implicated in the acute effects of ethanol. In this study, rats were trained to discriminate 1000mg/kg ethanol from saline. This dose of ethanol was consistently discriminated from saline but had no effects on overall rates of responding. Substitution tests were conducted with a number of GABA agonists and NMDA antagonists. Both midazolam and pentobarbital exhibited substantial substitution for ethanol at doses that moderately decreased response rates. However, muscimol and baclofen completely failed to substitute for ethanol, as did a combination of a fixed dose of muscimol with increasing doses of baclofen. The non-competitive NMDA antagonists PCP, dizocilpine and ketamine substituted fully for ethanol, but only at doses that also substantially suppressed rates of responding. The competitive NMDA antagonists, CPPene and NPC 17742, partially substituted for ethanol. The levels of substitution for ethanol among the indirect GABA agonists and the non-competitive NMDA antagonists indicate that the discriminative stimulus effects of ethanol, at least at a 1000mg/kg dose, may involve both GABAergic and glutamatergic systems.
乙醇的急性效应涉及γ-氨基丁酸（GABA）能神经传递的增强和涉及N-甲基-D-天冬氨酸（NMDA）受体的谷氨酸能神经传递的拮抗作用。在本研究中，训练大鼠区分1000mg/kg乙醇和生理盐水。该剂量的乙醇能持续与生理盐水区分开，但对整体反应率没有影响。用多种GABA激动剂和NMDA拮抗剂进行替代试验。咪达唑仑和戊巴比妥在适度降低反应率的剂量下对乙醇表现出显著的替代作用。然而，蝇蕈醇和巴氯芬完全不能替代乙醇，固定剂量的蝇蕈醇与递增剂量的巴氯芬联合使用时也是如此。非竞争性NMDA拮抗剂苯环己哌啶（PCP）、地佐环平（MK-801）和氯胺酮能完全替代乙醇，但仅在也能显著抑制反应率的剂量下才行。竞争性NMDA拮抗剂CPPene和NPC 17742能部分替代乙醇。间接GABA激动剂和非竞争性NMDA拮抗剂对乙醇的替代水平表明，至少在1000mg/kg剂量下，乙醇的辨别刺激效应可能涉及GABA能和谷氨酸能系统。
