Shen E H, Phillips T J
Department of Behavioral Neuroscience, Oregon Health Sciences University and Department of Veterans Affairs, Portland 97201, USA.
Pharmacol Biochem Behav. 1998 Jan;59(1):135-43. doi: 10.1016/s0091-3057(97)00389-4.
FAST vs. SLOW selected mouse lines and C57BL/6J (B6) vs. DBA/2J (D2) inbred strains differ in their sensitivities to ethanol's locomotor stimulant effects, and provide two unique sets of genetic animal models to study neurophysiological substrates of this behavior. To determine whether NMDA receptor function mediates sensitivity to ethanol's stimulant effects, we assessed the effects of the noncompetitive NMDA antagonist, MK-801, on locomotor activity of naive and ethanol-treated FAST, SLOW, B6, and D2 mice. MK-801 (0.01-0.5 mg/kg, I.P.) had biphasic effects in all genotypes, with stimulation at moderate doses and decreased activation at the highest dose. FAST mice were more activated by MK-801 than SLOW mice, suggesting that selection differentially altered NMDA receptor function between the lines. B6 and D2 mice did not differ in locomotor responses following MK-801 administration. Stimulant doses of MK-801 decreased or blocked ethanol-stimulated locomotor activity in FAST and D2 mice, and potentiated the locomotor depressant actions of ethanol in SLOW and B6 mice. Potentiation of ethanol's activating properties was observed in one treatment group in D2 mice. These data suggest that NMDA receptors modulate ethanol's stimulant properties, by a more significant involvement in expression of ethanol's locomotor depressant properties.
快速型与慢速型选择的小鼠品系以及近交系C57BL/6J（B6）与DBA/2J（D2）对乙醇的运动刺激作用敏感性不同，为研究这种行为的神经生理基础提供了两组独特的遗传动物模型。为了确定NMDA受体功能是否介导对乙醇刺激作用的敏感性，我们评估了非竞争性NMDA拮抗剂MK-801对未处理及经乙醇处理的快速型、慢速型、B6和D2小鼠运动活性的影响。MK-801（0.01 - 0.5毫克/千克，腹腔注射）对所有基因型均有双相作用，中等剂量时产生刺激作用，最高剂量时激活作用减弱。快速型小鼠比慢速型小鼠对MK-801的激活作用更敏感，这表明品系选择使两品系间的NMDA受体功能发生了差异改变。给予MK-801后，B6和D2小鼠的运动反应没有差异。刺激剂量的MK-801降低或阻断了快速型和D2小鼠中乙醇刺激的运动活性，并增强了慢速型和B6小鼠中乙醇的运动抑制作用。在D2小鼠的一个治疗组中观察到乙醇激活特性的增强。这些数据表明，NMDA受体通过更显著地参与乙醇运动抑制特性的表达来调节乙醇的刺激特性。
