GLUTAMATE-DOPAMINE INTERACTIONS IN THE VENTRAL STRIATUM - ROLE IN LOCOMOTOR-ACTIVITY AND RESPONDING WITH CONDITIONED REINFORCEMENT
GLUTAMATE-DOPAMINE INTERACTIONS IN THE VENTRAL STRIATUM - ROLE IN LOCOMOTOR-ACTIVITY AND RESPONDING WITH CONDITIONED REINFORCEMENT
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DOI：
10.1007/bf02245576
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发表时间：
1994-08-01
影响因子：
3.4
通讯作者：
ROBBINS, TW
中科院分区：
文献类型：
--
作者：
BURNS, LH;EVERITT, BJ;ROBBINS, TW
先前的证据表明，谷氨酸能边缘传入纤维参与了由伏隔核内d -安非他明产生的条件性强化反应的增强作用。本实验旨在研究腹侧纹状体中谷氨酸 - 多巴胺在条件性强化和运动活动方面的相互作用。谷氨酸受体激动剂和拮抗剂被单独或与3微克d -安非他明联合注入伏隔核，并测量这些相互作用对条件性强化反应和运动活动的影响。在这些研究中使用了谷氨酸受体激动剂N -甲基 - D -天冬氨酸（NMDA）、α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸（AMPA）和使君子氨酸（分别为NMDA、AMPA和代谢型谷氨酸受体亚型的激动剂）以及拮抗剂2 - 氨基 - 5 - 磷酰基戊酸（AP5）和6 - 氰基 - 7 - 硝基喹喔啉 - 2,3 - 二酮（CNQX，分别为NMDA和AMPA受体亚型的拮抗剂）。除CNQX使用0.2至2纳摩尔剂量外，这些化合物的使用剂量范围为0.3至3纳摩尔。虽然所有激动剂和拮抗剂单独给药时都会增加运动活动，但拮抗剂会减弱对d -安非他明的运动反应。相比之下，激动剂AMPA和使君子氨酸增强了d -安非他明诱导的运动活动，尽管NMDA干扰了d -安非他明的作用。在条件性强化范式中，激动剂和拮抗剂都消除了安非他明对条件性强化反应的增强作用，这表明关于条件性强化物的谷氨酸能信息传递可被谷氨酸受体拮抗剂阻断，并被激动剂的使用所干扰。这些兴奋性氨基酸对安非他明诱导的运动活动的影响与其对安非他明增强条件性强化反应的影响之间的分离，为了解伏隔核多巴胺的奖赏增强作用与其运动刺激作用的性质提供了见解。
Previous evidence suggests that glutamatergic limbic afferents participate in the potentiation of responding with conditioned reinforcement produced by intra-accumbens d-amphetamine. The present experiments were designed to investigate glutamate-dopamine interactions in the ventral striatum in both conditioned reinforcement and locomotor activity. Glutamate receptor agonists and antagonists were infused into the nucleus accumbens both alone and in combination with 3 mu g d-amphetamine, and the effects of these interactions on responding with conditioned reinforcement and locomotor activity were measured. The glutamate receptor agonists NMDA, AMPA and quisqualate (agonists at the NMDA, AMPA and metabotropic glutamate receptor subtypes, respectively) and the antagonists AP5 and CNQX, (antagonists at the NMDA and AMPA receptor subtypes, respectively) were used in these investigations. These compounds were used in a dose range of 0.3 to 3 nmol, except CNQX, which was used in 0.2 to 2 nmol doses. While all agonists and antagonists increased locomotor activity when administered alone, the antagonists attenuated the locomotor response to d-amphetamine. In contrast, the agonists AMPA and quisqualate enhanced d-amphetamine-induced locomotor activity, although NMDA interfered with the effects of d-amphetamine. In the conditioned reinforcement paradigm, both the agonists and the antagonists abolished amphetamine's potentiation of responding with conditioned reinforcement, suggesting that the glutamatergic transmission of information about the conditioned reinforcer could be blocked by glutamate receptor antagonists and disrupted by administration of the agonists. The dissociation between the effects of these excitatory amino acids on amphetamine-induced locomotor activity versus their effects on amphetamine's potentiation of responding with conditioned reinforcement provides insight into the nature of the reward enhancement by accumbens dopamine versus its locomotor stimulant effects.