Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons
Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons
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DOI：
10.1038/35079077
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发表时间：
2001-05-31
期刊：
影响因子：
64.8
通讯作者：
Bonci, A
中科院分区：
文献类型：
--
作者：
Ungless, MA;Whistler, JL;Bonci, A
滥用药物如何改变神经回路，从而导致成瘾行为？对于许多形式的经验依赖性可塑性，在突触传递中的修饰被认为是特别重要的（1-4）。然而，缺乏对滥用药物体内给药作出反应的这种变化的证据。在这里，我们表明，一个单一的在体内暴露于可卡因诱导长期增强AMPA（α-氨基-3-羟基-5-甲基异恶唑丙酸）受体介导的电流在兴奋性突触到多巴胺细胞在腹侧被盖区。在可卡因暴露后5天而不是10天仍然观察到增强作用，并且当NMDA（N-甲基-D-天冬氨酸）受体拮抗剂与可卡因一起施用时被阻断。此外，在这些突触的长时程增强闭塞和长期抑郁症是增强体内可卡因暴露。这些结果表明，一个突出的形式的突触可塑性可以引起一个单一的体内暴露于可卡因，因此可能参与药物成瘾的发展的早期阶段。
How do drugs of abuse modify neural circuitry and thereby lead to addictive behaviour? As for many forms of experience-dependent plasticity, modifications in glutamatergic synaptic transmission have been suggested to be particularly important(1-4). Evidence of such changes in response to in vivo administration of drugs of abuse is lacking, however. Here we show that a single in vivo exposure to cocaine induces long-term potentiation of AMPA (alpha -amino-3-hydroxy-5-methyl-isoxazole propionic acid)-receptor-mediated currents at excitatory synapses onto dopamine cells in the ventral tegmental area. Potentiation is still observed 5 but not 10 days after cocaine exposure and is blocked when an NMDA (N-methyl-D-aspartate) receptor antagonist is administered with cocaine. Furthermore, long-term potentiation at these synapses is occluded and long-term depression is enhanced by in vivo cocaine exposure. These results show that a prominent form of synaptic plasticity can be elicited by a single in vivo exposure to cocaine and therefore may be involved in the early stages of the development of drug addiction.