Glutamate-associated plasticity in the ventral tegmental area is necessary for conditioning environmental stimuli with morphine
Glutamate-associated plasticity in the ventral tegmental area is necessary for conditioning environmental stimuli with morphine
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DOI：
10.1016/j.neuroscience.2004.09.018
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Aston-Jones, G
中科院分区：
文献类型：
--
作者：
Harris, GC;Wimmer, M;Aston-Jones, G
我们试图确定中脑腹侧被盖区（VTA）的可塑性是否与学习将吗啡暴露与特定环境联系起来有关。为此，我们测试了吗啡条件性位置偏好 (CPP) 的获得和表达是否需要谷氨酸受体和蛋白激酶 A 的激活。在三个吗啡调节疗程中的每一个疗程之前，大鼠在 VTA 中接受 NMDA 拮抗剂 AP5（0.48 nmol/0.3 mul）、AMPA 拮抗剂 CNQX（0.21 nmol/0.3 mul）或媒介物的双侧显微注射。 AMPA 和 NMDA 受体拮抗剂在 VTA 内给药时均可阻断吗啡 CPP 的发展，但在 VTA 外给药时则不会。在类似的研究中，在吗啡调理后立即给予 VTA 时，蛋白激酶 A (PKA) 抑制剂 Rp-cAMPS (13 nmol/0.3 μl) 会阻止吗啡 CPP 的获取。在单独的实验中，在偏好测试之前，将谷氨酸拮抗剂或 Rp-cAMPS 显微注射到 VTA 中时，会阻断吗啡 CPP 的表达。这些数据表明，VTA 是突触修饰的重要部位，涉及预测奖励的环境线索的学习和记忆，并且谷氨酸输入和 PKA 激活对此过程至关重要。 (C) 2004 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
We sought to determine if plasticity in the ventral tegmental area (VTA) of the midbrain is involved in learning to associate morphine exposure with a specific environment. For this, we tested whether activation of glutamate receptors and protein kinase A is needed for the acquisition and expression of a morphine-conditioned place preference (CPP). Rats received bilateral microinjections of either the NMDA antagonist AP5 (0.48 nmol/0.3 mul), the AMPA antagonist CNQX (0.21 nmol/0.3 mul), or vehicle into the VTA prior to each of three morphine-conditioning sessions. Both the AMPA and NMDA receptor antagonists blocked the development of morphine CPP when given into the VTA but not when given outside the VTA. In similar studies the protein kinase A (PKA) inhibitor, Rp-cAMPS (13 nmol/0.3 mul), blocked the acquisition of morphine CPP when given into the VTA immediately after morphine conditioning. In separate experiments, glutamate antagonists, or Rp-cAMPS, immediately prior to the preference test blocked the expression of morphine CPP when microinjected into the VTA. These data indicate that the VTA is an important site for synaptic modifications involved in the learning and memory of environmental cues predicting reward, and that glutamate input and PKA activation are crucial to this process. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.