Ouagazzal A, Nieoullon A, Amalric M
Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, CNRS, Marseille, France.
Psychopharmacology (Berl). 1993;111(4):427-34. doi: 10.1007/BF02253532.
Blocking glutamatergic transmission at the N-methyl-D-aspartate (NMDA) receptor complex with MK-801 (0.15-0.5 mg/kg, IP) was found to induce a robust, dose-dependent increase in locomotor activity. This behavioural activation was similar in intensity to that observed after d-amphetamine (1 mg/kg, SC). The locomotor stimulation induced by MK-801 at 0.3 mg/kg was significantly inhibited by the D2 dopamine receptor antagonist raclopride (0.1-0.3 mg/kg, SC) and by the D1 receptor antagonist SCH 23390 (0.04 mg/kg, SC). The locomotor activity induced by a higher dose of MK-801 (0.5 mg/kg) was reduced by higher doses of raclopride or SCH 23390 administered alone (0.3 and 0.08 mg/kg, respectively), and was inhibited by simultaneous administration of ineffective doses. Raclopride significantly reduced d-amphetamine-induced locomotor activity at a dose (0.2 mg/kg) that also blocked the effects of a low dose of MK-801. In contrast, SCH 23390 blocked the effects of d-amphetamine at a dose (i.e. 0.01 mg/kg) lower than that needed to block MK-801. These results suggest that the dopaminergic system may in part mediate the locomotor effects induced by the NMDA antagonist, MK-801, in rats. However, the locomotor activity induced by MK-801 appears to be less sensitive to dopaminergic receptor blockade than that induced by d-amphetamine, suggesting that the underlying mechanisms, although similar, are not identical.
研究发现，用MK-801（0.15 - 0.5毫克/千克，腹腔注射）阻断N-甲基-D-天冬氨酸（NMDA）受体复合物处的谷氨酸能传递，会导致自发活动显著增强，且呈剂量依赖性。这种行为激活的强度与注射d-苯丙胺（1毫克/千克，皮下注射）后观察到的相似。0.3毫克/千克的MK-801诱导的自发活动增强，被D2多巴胺受体拮抗剂雷氯必利（0.1 - 0.3毫克/千克，皮下注射）和D1受体拮抗剂SCH 23390（0.04毫克/千克，皮下注射）显著抑制。更高剂量（0.5毫克/千克）的MK-801诱导的自发活动，单独给予更高剂量的雷氯必利或SCH 23390（分别为0.3和0.08毫克/千克）会降低，同时给予无效剂量时则被抑制。雷氯必利在0.2毫克/千克的剂量下显著降低了d-苯丙胺诱导的自发活动，该剂量也阻断了低剂量MK-801的作用。相比之下，SCH 23390在低于阻断MK-801所需的剂量（即0.01毫克/千克）时就阻断了d-苯丙胺的作用。这些结果表明，多巴胺能系统可能部分介导了NMDA拮抗剂MK-801在大鼠中诱导的自发活动效应。然而，MK-801诱导的自发活动似乎对多巴胺能受体阻断的敏感性低于d-苯丙胺诱导的，这表明潜在机制虽然相似，但并不相同。
