Stuber Garret D, Hopf F Woodward, Tye Kay M, Chen Billy T, Bonci Antonello
Department of Neurology, University of California, San Francisco, CA, USA.
Curr Top Behav Neurosci. 2010;3:3-27. doi: 10.1007/7854_2009_23.
Neuroplastic changes in the CNS are thought to be a fundamental component of learning and memory. While pioneering studies in the hippocampus and cerebellum have detailed many of the basic mechanisms that can lead to alterations in synaptic transmission based on previous activity, only more recently has synaptic plasticity been monitored after behavioral manipulation or drug exposure. In this chapter, we review evidence that drugs of abuse are powerful modulators of synaptic plasticity. Both the dopaminergic neurons of the ventral tegmental area as well medium spiny neurons in nucleus accumbens show enhanced excitatory synaptic strength following passive or active exposure to drugs such as cocaine and alcohol. In the VTA, both the enhancement of excitatory synaptic strength and the acquisition of drug-related behaviors depend on signaling through the N-methyl-D: -aspartate receptors (NMDARs) which are mechanistically thought to lead to increased synaptic insertion of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Synaptic insertion of AMPARs by drugs of abuse can be long lasting, depending on the route of administration, number of drug exposures, or whether the drugs are received passively or self-administered.
中枢神经系统中的神经可塑性变化被认为是学习和记忆的基本组成部分。虽然在海马体和小脑进行的开创性研究已经详细阐述了许多基于先前活动可导致突触传递改变的基本机制，但直到最近才在行为操纵或药物暴露后监测突触可塑性。在本章中，我们回顾了证据表明滥用药物是突触可塑性的强大调节剂。腹侧被盖区的多巴胺能神经元以及伏隔核中的中等棘状神经元在被动或主动接触可卡因和酒精等药物后均表现出增强的兴奋性突触强度。在腹侧被盖区，兴奋性突触强度的增强和与药物相关行为的习得都依赖于通过N-甲基-D-天冬氨酸受体（NMDARs）的信号传导，从机制上认为这会导致α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPARs）在突触处的插入增加。滥用药物导致的AMPARs在突触处的插入可以是持久的，这取决于给药途径、药物暴露次数，或者药物是被动接受还是自我给药。
