Svensson A, Carlsson A, Carlsson M L
Department of Pharmacology, University of Göteborg, Sweden.
J Neural Transm Gen Sect. 1992;90(3):199-217. doi: 10.1007/BF01250961.
Previous work in our laboratory has shown that the non-competitive N-methyl-D-aspartate antagonist dizocilipine (MK-801) interacts synergistically with the mixed dopamine (DA) receptor agonist apomorphine and the DA D 1 agonist SKF 38393 to promote locomotion in monoamine-depleted mice. The purpose of the present study was to compare the roles of DA D 1 and DA D 2 receptors in this interaction. To that end, dizocilpine was given in combination with either the DA D 1 receptor agonist SKF 38393 or the selective DA D 2 receptor agonist quinpirole or the preferential DA D 2 agonist bromocriptine. In general, the locomotor stimulatory effects produced by SKF 38393 were potentiated by dizocilpine, whereas the locomotor stimulation produced by quinpirole and bromocriptine was counteracted. However, baseline activity, which partly depends on how much time is allowed to elapse between administration of the DA agonist and commencement of locomotor recording, and partly on the dose of the DA agonist, seems to be an important factor that determines whether dizocilpine will have a weakening or a potentiating effect. Interestingly, the competitive NMDA antagonist D-CPPene displayed a different pattern of interaction with SKF 38393 and quinpirole in that synergistic effects were observed with both DA agonists, most conspicuously so with the DA D 2 receptor agonist. The results are interpreted in the light of present knowledge of basal ganglia neuroanatomy; they are discussed in relation to the "direct" and "indirect" pathways from the striatum to the thalamus, proposed to form part of positive and negative cortico-striato-thalamo-cortical loops, respectively, as well as to the presumed presynaptic D 2 receptors on corticostriatal glutamatergic neurons.
我们实验室之前的研究表明，非竞争性N-甲基-D-天冬氨酸拮抗剂地佐环平（MK-801）与混合多巴胺（DA）受体激动剂阿扑吗啡及DA D1激动剂SKF 38393协同作用，可促进单胺耗竭小鼠的运动。本研究的目的是比较DA D1和DA D2受体在这种相互作用中的作用。为此，将地佐环平与DA D1受体激动剂SKF 38393、选择性DA D2受体激动剂喹吡罗或优先性DA D2激动剂溴隐亭联合使用。一般来说，SKF 38393产生的运动刺激作用被地佐环平增强，而喹吡罗和溴隐亭产生的运动刺激作用则被抵消。然而，基线活动似乎是一个重要因素，它部分取决于给予DA激动剂与开始运动记录之间的时间间隔，部分取决于DA激动剂的剂量，这决定了地佐环平是产生减弱作用还是增强作用。有趣的是，竞争性NMDA拮抗剂D-CPPene与SKF 38393和喹吡罗表现出不同的相互作用模式，即与两种DA激动剂均观察到协同作用，与DA D2受体激动剂的协同作用最为显著。根据目前对基底神经节神经解剖学的了解对结果进行了解释；结合从纹状体到丘脑的“直接”和“间接”通路进行了讨论，这两条通路分别被认为是正性和负性皮质-纹状体-丘脑-皮质环路的一部分，同时也涉及皮质纹状体谷氨酸能神经元上假定的突触前D2受体。
