Dopamine D-1/D-5 receptor activation is required for long-term potentiation in the rat neostriatum in vitro
Dopamine D-1/D-5 receptor activation is required for long-term potentiation in the rat neostriatum in vitro
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DOI：
10.1152/jn.2001.85.1.117
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发表时间：
2001-01-01
影响因子：
2.5
通讯作者：
Wickens, JR
中科院分区：
文献类型：
--
作者：
Kerr, JND;Wickens, JR
多巴胺和谷氨酸是大脑学习和记忆机制中的关键神经递质。这两个神经递质系统汇聚在新纹状体的神经细胞上。多巴胺对谷氨酸能皮质纹状体突触活动依赖性可塑性的调节被认为是新纹状体学习的一种细胞机制。本研究利用皮质纹状体切片制备中纹状体神经元的细胞内记录，研究了特定亚型多巴胺受体在皮质纹状体通路长时程增强(LTP)中的作用。与以前的报道一致，在无镁条件下可以可靠地诱导LTP。这种无镁长时程增强可被多巴胺耗竭和多巴胺D-1/D-5受体拮抗剂SCH 23390阻断，但不能被多巴胺D-2受体拮抗剂RemxiPride或GABA(A)拮抗剂印防己毒素阻断。在多巴胺耗竭的脑片中，可以通过沐浴应用多巴胺D-1/D-5受体激动剂SKF 38393来恢复诱导LTP的能力。这些结果表明，内源性或外源性多巴胺激动剂激活多巴胺D-1/D-5受体是诱导皮质纹状体通路长时程增强的必要条件。这些发现对于目前理解新纹状体的学习和记忆机制，以及从理论上理解治疗精神病和帕金森病的药物的作用机制具有重要意义。
Dopamine and glutamate are key neurotransmitters involved in learning and memory mechanisms of the brain. These two neurotransmitter systems converge on nerve cells in the neostriatum. Dopamine modulation of activity-dependent plasticity at glutamatergic corticostriatal synapses has been proposed as a cellular mechanism for learning in the neostriatum. The present research investigated the role of specific subtypes of dopamine receptors in long-term potentiation (LTP) in the corticostriatal pathway, using intracellular recording from striatal neurons in a corticostriatal slice preparation. In agreement with previous reports, LTP could be induced reliably under Mg2+-free conditions. This Mg2+-free LTP was blocked by dopamine depletion and by the dopamine D-1/D-5 receptor antagonist SCH 23390 but was not blocked by the dopamine D-2 receptor antagonist remoxipride or the GABA(A) antagonist picrotoxin. In dopamine-depleted slices, the ability to induce LTP could be restored by bath application of the dopamine D-1/D-5 receptor agonist, SKF 38393. These results show that activation of dopamine D-1/D-5 receptors by either endogenous dopamine or exogenous dopamine agonists is a requirement for the induction of LTP in the corticostriatal pathway. These findings have significance for current understanding of learning and memory mechanisms of the neostriatum and for theoretical understanding of the mechanism of action of drugs used in the treatment of psychotic illnesses and Parkinson's disease.