Modulation of the mesolimbic dopamine system by glutamate: Role of NMDA receptors
Modulation of the mesolimbic dopamine system by glutamate: Role of NMDA receptors
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DOI：
10.1046/j.1471-4159.1999.0730839.x
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发表时间：
1999-08-01
影响因子：
4.7
通讯作者：
Kretschmer, BD
中科院分区：
文献类型：
--
作者：
Kretschmer, BD
谷氨酸可能通过N-甲基-D-天冬氨酸（NMDA）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体调节运动行为，这些受体参与中脑边缘多巴胺（DA）系统的控制，即腹侧被盖区（VTA）-中脑背核（NAC）。我们研究了非竞争性（MK-801）和竞争性[DL-2-氨基-5-膦酰基戊酸（AP-5），CGP 40116] NMDA受体拮抗剂以及NMDA和AMPA对中脑边缘系统中DA释放和运动行为的影响。MK-801的全身注射和被盖内输注增加了VTA中的DA水平，但全身给药仅增强了NAC中的DA，并增加了运动行为。与此相反，被盖内注入AP-5，而不是其亲脂性类似物CGP 40116的全身给药，降低了DA释放在这两个地区，而不影响运动行为。NMDA和AMPA注入VTA增加了这两个领域的DA水平。这种增加伴随着强烈的运动行为刺激后，NMDA，但只有一个温和的增加后，AMPA输液，目前的结果表明，中脑边缘DA神经元的神经元控制的多巴胺能系统和非竞争性和竞争性的NMDA受体拮抗剂对DA释放的影响是通过与不同的脑区的相互作用介导的。这些发现可能解释了NMDA受体配体对运动行为的不同影响。
Glutamate has been shown to modulate motor behavior, probably via N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that are involved in the control of the mesolimbic dopamine (DA) system, that is, the ventral tegmental area (VTA)-nucleus accumbens (NAC), In the present study, we investigated the effects of uncompetitive (MK-801) and competitive [DL-2-amino-5-phosphonopentanoic acid (AP-5), CGP 40116] NMDA receptor antagonists and NMDA and AMPA on DA release in the mesolimbic system and on motor behavior. Systemic injection and intrategmental infusion of MK-801 increased DA levels in the VTA, but the systemic administration enhanced DA exclusively in the NAC and increased motor behavior. In contrast, intrategmental infusion of AP-5, but not the systemic administration of its lipophilic analogue CGP 40116, decreased the DA release in the two regions without affecting motor behavior. NMDA and AMPA infusion into the VTA increased DA levels in both areas. This increase was accompanied by a strong motor behavioral stimulation after NMDA but only a moderate increase after AMPA infusion, The present results indicate that mesolimbic DA neurons are controlled by the glutamatergic system and that the effects of uncompetitive and competitive NMDA receptor antagonists on DA release are mediated by an interaction with different brain areas. These findings may account for the different effects of NMDA receptor ligands on motor behavior.