Ogren S O, Goldstein M
Karolinska Institute, Department of Histology and Neurobiology, Stockholm, Sweden.
Neuropsychopharmacology. 1994 Nov;11(3):167-77. doi: 10.1038/sj.npp.1380103.
The dopamine (DA) D2 agonist quinpirole and the D2 receptor antagonists, haloperidol, raclopride, and remoxipride, were examined for their ability to block the locomotion induced by the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists phencyclidine (PCP) and dizocilpine, both given in equipotent doses. Quinpirole, given in a "DA D2 autoreceptor selective" dose (0.01 mg/kg), failed to influence the motor stimulation by PCP. On the other hand, the locomotor response induced by dizocilpine was significantly reduced by quinpirole. The three DA receptor antagonists blocked dose dependently the motor stimulation produced by both the low (2 mg/kg) and the high dose (3 mg/kg) of PCP. Haloperidol and remoxipride also blocked dose dependently and fully the stimulation produced by the low dose (0.1 mg/kg) of dizocilpine, whereas raclopride partially reduced the effect. The motor stimulation produced by the high doses of dizocilpine (0.2 mg/kg) and PCP (3 mg/kg) was reduced by haloperidol and raclopride only in cataleptogenic doses. Remoxipride, in contrast, fully blocked the effects of both PCP (3 mg/kg) and dizocilpine (0.2 mg/kg) in noncataleptogenic doses. These data suggest that different mechanisms of action may account for the motor stimulatory effects of PCP and dizocilpine. At the presynaptic level, PCP and dizocilpine may differ in the way they act on "regulatory" NMDA receptors controlling neuronal activity in midbrain neurons, and at the postsynaptic level they may interact with subtypes of NMDA receptors differentially coupled to subpopulations of D2 receptors.
研究了多巴胺（DA）D2激动剂喹吡罗以及D2受体拮抗剂氟哌啶醇、雷氯必利和瑞莫必利阻断非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂苯环己哌啶（PCP）和地佐环平诱导的运动的能力，二者均给予等效剂量。以“DA D2自身受体选择性”剂量（0.01 mg/kg）给予的喹吡罗未能影响PCP诱导的运动刺激。另一方面，喹吡罗可显著降低地佐环平诱导的运动反应。三种DA受体拮抗剂均剂量依赖性地阻断低剂量（2 mg/kg）和高剂量（3 mg/kg）PCP产生的运动刺激。氟哌啶醇和瑞莫必利也剂量依赖性且完全地阻断低剂量（0.1 mg/kg）地佐环平产生的刺激，而雷氯必利仅部分降低该效应。仅在致僵剂量下，氟哌啶醇和雷氯必利可降低高剂量地佐环平（0.2 mg/kg）和PCP（3 mg/kg）产生的运动刺激。相比之下，瑞莫必利在非致僵剂量下可完全阻断PCP（3 mg/kg）和地佐环平（0.2 mg/kg）的作用。这些数据表明，不同的作用机制可能解释了PCP和地佐环平的运动刺激作用。在突触前水平，PCP和地佐环平在作用于控制中脑神经元神经活动的“调节性”NMDA受体的方式上可能存在差异，而在突触后水平，它们可能与不同亚型的NMDA受体相互作用，这些受体与不同亚群的D2受体偶联。
