Department of Molecular Neuropharmacology, Institute of Pharmacology of the Polish Academy of Sciences Krakow, Poland.
Front Mol Neurosci. 2012 Aug 31;5:89. doi: 10.3389/fnmol.2012.00089. eCollection 2012.
Drug-induced changes in the functional properties of neurons in the mesolimbic dopaminergic system are attractive candidates for the molecular underpinnings of addiction. A central question in this context has been how drugs of abuse affect synaptic plasticity on dopaminergic cells in the ventral tegmental area. We now know that the intake of addictive drugs is accompanied by a complex sequence of alterations in the properties of excitatory synapses on dopaminergic neurons, mainly driven by signaling and redistribution of NMDA- and AMPA-receptors. It has, however, been unclear how these molecular changes are related to the behavioral effects of addictive drugs. Recently, new genetic tools have permitted researchers to perform genetic intervention with plasticity-related molecules selectively in dopaminergic cells and to subsequently study the behaviors of genetically modified mice. These studies have started to reveal how plasticity and drug-induced behavior are connected as well as what role plasticity in dopaminergic cells may have in general reward learning. The findings thus far show that there is not a one-to-one relation between plastic events and specific behaviors and that the early responses to drugs of abuse are to a large extent independent of the types of synaptic plasticity so far targeted. In contrast, plasticity in dopaminergic cells indeed is an important regulator of the persistence of behaviors driven by drug associations, making synaptic plasticity in dopaminergic cells an important field of study for understanding the mechanisms behind relapse.
药物诱导的中脑边缘多巴胺能系统神经元功能特性的改变是成瘾的分子基础的有吸引力的候选者。在这方面的一个核心问题是，滥用药物如何影响腹侧被盖区多巴胺能细胞的突触可塑性。我们现在知道，成瘾药物的摄入伴随着多巴胺能神经元上兴奋性突触特性的一系列复杂变化，主要由 NMDA 和 AMPA 受体的信号转导和重新分布驱动。然而，这些分子变化与成瘾药物的行为效应如何相关尚不清楚。最近，新的遗传工具允许研究人员选择性地在多巴胺能细胞中对与可塑性相关的分子进行遗传干预，然后研究基因修饰小鼠的行为。这些研究开始揭示可塑性和药物诱导的行为是如何联系的，以及多巴胺能细胞中的可塑性在一般奖励学习中可能起什么作用。迄今为止的发现表明，塑性事件与特定行为之间没有一一对应的关系，而且滥用药物的早期反应在很大程度上独立于迄今为止针对的突触可塑性类型。相比之下，多巴胺能细胞中的可塑性确实是由药物关联驱动的行为持续存在的重要调节剂，这使得多巴胺能细胞中的突触可塑性成为理解复发背后机制的一个重要研究领域。
