Critical role for ventral tegmental glutamate in preference for a cocaine-conditioned environment
Critical role for ventral tegmental glutamate in preference for a cocaine-conditioned environment
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DOI：
10.1038/sj.npp.1300011
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发表时间：
2003-01-01
影响因子：
7.6
通讯作者：
Aston-Jones, G
中科院分区：
文献类型：
--
作者：
Harris, GC;Aston-Jones, G
可卡因给药会诱导中脑边缘-伏隔系统内的谷氨酸能激活。这种激活与可卡因的行为效应有关，最近还与腹侧被盖区（VTA）内多巴胺神经元的长期增强的诱导有关。我们试图确定谷氨酸受体激活是否对于可卡因奖励效应的条件性位置偏好（CPP）的发展也至关重要。在每次可卡因位置调节试验之前，两组大鼠在 VTA 内注射媒介物或 NMDA（N-甲基-D-天冬氨酸）和 AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）受体拮抗剂（AP5 0.24 nmol 加 CNQX 0.12 nmol 每侧）的组合。当在 VTA 内注射谷氨酸拮抗剂时，微量注射可完全阻止可卡因 CPP 的形成，但在 VTA 外注射则不会。这些数据表明，VTA 中的谷氨酸活性对于学习将环境刺激与可卡因暴露联系起来可能至关重要。
Cocaine administration induces glutamatergic activation within the mesolimbic-accumbens system. This activation has been linked to the behavioral effects of cocaine and recently to the induction of long-term potentiation in dopamine neurons within the ventral tegmental area (VTA). We sought to determine if glutamate receptor activation is also crucial to the development of a conditioned place preference (CPP) to cocaine's rewarding effects. Two groups of rats were given intra-VTA injections of either vehicle or a combination of NMDA (N-methyl-D-aspartate) and AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonists (AP5 0.24 nmol plus CNQX 0.12 nmol per side) prior to each cocaine place-conditioning trial. Microinjections of the glutamate antagonists completely blocked the development of a cocaine CPP when given within, but not when given outside of, the VTA. These data indicate that glutamatergic activity in the VTA may be crucial for learning to associate environmental stimuli with cocaine exposure.