Liljequist S, Ossowska K, Grabowska-Andén M, Andén N E
Department of Drug Dependence Research, Karolinska Institute, Stockholm, Sweden.
Eur J Pharmacol. 1991 Mar 19;195(1):55-61. doi: 10.1016/0014-2999(91)90381-y.
Various doses (0.1-0.5 mg/kg i.p.) of the N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, produced a dose-dependent increase in well-coordinated locomotor activity of NMRI mice. Higher doses (greater than 0.5 mg/kg) produced a typical motor syndrome characterized by head weaving, body rolling, ataxia and salivation. MK-801, 0.2 mg/kg i.p., a dose which produced marked locomotor stimulation, increased the rate of disappearance of dopamine in the striatum and in the limbic forebrain of the animals, whereas the rate of disappearance of noradrenaline remained unchanged in the limbic forebrain and in the hippocampus. MK-801 increased the rate of tyrosine hydroxylation (measured as the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after inhibition of DOPA decarboxylase) in the striatum with no change in DOPA formation in the limbic forebrain. The levels of 3,4-dihydroxyphenylacetic acid (DOPAC) remained unchanged both in the striatum and in the limbic forebrain following the administration of MK-801. It is concluded that MK-801 may facilitate the activation of dopaminergic mechanisms through an indirect (perhaps by reducing glutamatergic activity) rather than a direct effect on dopamine neurons.
不同剂量（腹腔注射0.1 - 0.5毫克/千克）的N - 甲基 - D - 天冬氨酸（NMDA）受体拮抗剂MK - 801，可使NMRI小鼠的协调性运动活动呈剂量依赖性增加。更高剂量（大于0.5毫克/千克）会产生典型的运动综合征，其特征为头部摆动、身体翻滚、共济失调和流涎。腹腔注射0.2毫克/千克的MK - 801，这一剂量可产生明显的运动刺激，增加了动物纹状体和边缘前脑中多巴胺的消失速率，而去甲肾上腺素在边缘前脑和海马体中的消失速率保持不变。MK - 801增加了纹状体中酪氨酸羟化作用的速率（通过抑制多巴脱羧酶后测量3,4 - 二羟基苯丙氨酸（DOPA）的积累来衡量），而边缘前脑中DOPA的形成没有变化。给予MK - 801后，纹状体和边缘前脑中3,4 - 二羟基苯乙酸（DOPAC）的水平均保持不变。得出的结论是，MK - 801可能通过间接方式（可能是通过降低谷氨酸能活性）而非直接作用于多巴胺神经元来促进多巴胺能机制的激活。
