David Hélène N, Sissaoui Kheira, Abraini Jacques H
Université de Caen Basse-Normandie, UMR CNRS 6551, IFR 47, Centre CYCERON, BP5229, Boulevard Henri Becquerel, 14074 Caen, cedex, France.
Neuropharmacology. 2004 Feb;46(2):179-91. doi: 10.1016/j.neuropharm.2003.08.009.
Dopamine and glutamate interactions in the nucleus accumbens (NAcc) play a crucial role in both the development of a motor response suitable for the environment and in the mechanisms underlying the motor-activating properties of psychostimulant drugs such as amphetamine. We investigated the effects of the infusion in the NAcc of NMDA and non-NMDA receptor agonists and antagonists on the locomotor responses induced by the selective D(1)-like receptor agonist SKF 38393, the selective D(2)-like receptor agonist quinpirole, alone or in combination, and D-amphetamine. Infusion of either the NMDA receptor agonist NMDA, the NMDA receptor antagonist D-AP5, the non-NMDA receptor antagonist CNQX, or the non-NMDA receptor agonist AMPA resulted in an increase in basal motor activity. Conversely, all of these ionotropic glutamate (iGlu) receptor ligands reduced the increase in locomotor activity induced by focal infusion of D-amphetamine. Interactions with dopamine receptor activation were not so clear: (i). infusion of NMDA and D-AP5 respectively enhanced and reduced the increase in locomotor activity induced by the infusion of the D(1)-like receptor agonist of SKF 38393, while AMPA or CNQX decreased it; (ii). infusion of NMDA, D-AP5, and CNQX reduced the increase in locomotor activity induced by co-injection of SKF 38393+quinpirole--a pharmacological condition thought to activate both D(1)-like and D(2)-like presynaptic and postsynaptic receptors, while infusion of AMPA potentiated it; (iii). infusion of either NMDA, D-AP5 or CNQX, but not of AMPA, potentiated the decrease in motor activity induced by the D(2)-like receptor agonist quinpirole, a compound believed to act only at presynaptic D(2)-like receptors when injected by itself. Our results show that NMDA receptors have an agonist action with D(1)-like receptors and an antagonist action with D(2)-like receptors, while non-NMDA receptors have the opposite action. This is discussed from a anatamo-functional point of view.
伏隔核（NAcc）中的多巴胺与谷氨酸相互作用在形成适合环境的运动反应以及诸如苯丙胺等精神兴奋药物的运动激活特性背后的机制中都起着关键作用。我们研究了向伏隔核中注入NMDA和非NMDA受体激动剂及拮抗剂对由选择性D(1)样受体激动剂SKF 38393、选择性D(2)样受体激动剂喹吡罗单独或联合使用以及D-苯丙胺诱导的运动反应的影响。注入NMDA受体激动剂NMDA、NMDA受体拮抗剂D-AP5、非NMDA受体拮抗剂CNQX或非NMDA受体激动剂AMPA均导致基础运动活动增加。相反，所有这些离子型谷氨酸（iGlu）受体配体都减少了局部注入D-苯丙胺所诱导的运动活动增加。与多巴胺受体激活的相互作用并不那么明确：（i）. 注入NMDA和D-AP5分别增强和降低了注入SKF 38393这种D(1)样受体激动剂所诱导的运动活动增加，而AMPA或CNQX则使其降低；（ii）. 注入NMDA、D-AP5和CNQX减少了共同注射SKF 38393 + 喹吡罗所诱导的运动活动增加——这是一种被认为能激活D(1)样和D(2)样突触前和突触后受体的药理学状态，而注入AMPA则使其增强；（iii）. 注入NMDA、D-AP5或CNQX中的任何一种，但不是AMPA，增强了由D(2)样受体激动剂喹吡罗诱导的运动活动减少，喹吡罗单独注射时被认为仅作用于突触前D(2)样受体。我们的结果表明，NMDA受体与D(1)样受体具有激动剂作用，与D(2)样受体具有拮抗剂作用，而非NMDA受体则具有相反的作用。从解剖学 - 功能学角度对此进行了讨论。
