Transition to Addiction Is Associated with a Persistent Impairment in Synaptic Plasticity
Transition to Addiction Is Associated with a Persistent Impairment in Synaptic Plasticity
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DOI：
10.1126/science.1187801
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发表时间：
2010-06-25
期刊：
影响因子：
56.9
通讯作者：
Piazza, Pier Vincenzo
中科院分区：
文献类型：
--
作者：
Kasanetz, Fernando;Deroche-Gamonet, Veronique;Piazza, Pier Vincenzo
长期接触滥用药物会导致大脑生理学的无数变化。然而，神经生物学适应具体与过渡到成瘾是未知的。皮质醇自身给药可迅速抑制长时程抑制（LTD），这是丘脑核中突触可塑性的一种重要形式。使用大鼠成瘾模型，我们发现，逐渐发展成瘾行为标志的动物永久性损害LTD，而LTD在保持受控药物摄入的非成瘾大鼠中逐渐恢复。通过使药物寻求持续抵抗环境突发事件的调节，从而变得越来越不灵活，持续受损的LTD可以介导向成瘾的过渡。
Chronic exposure to drugs of abuse induces countless modifications in brain physiology. However, the neurobiological adaptations specifically associated with the transition to addiction are unknown. Cocaine self-administration rapidly suppresses long-term depression (LTD), an important form of synaptic plasticity in the nucleus accumbens. Using a rat model of addiction, we found that animals that progressively develop the behavioral hallmarks of addiction have permanently impaired LTD, whereas LTD is progressively recovered in nonaddicted rats maintaining a controlled drug intake. By making drug seeking consistently resistant to modulation by environmental contingencies and consequently more and more inflexible, a persistently impaired LTD could mediate the transition to addiction.