Dietz D M, Dietz K C, Nestler E J, Russo S J
Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York 10029, USA.
Pharmacopsychiatry. 2009 May;42 Suppl 1(Suppl 1):S69-78. doi: 10.1055/s-0029-1202847. Epub 2009 May 11.
Drug addiction is characterized by persistent behavioral and cellular plasticity throughout the brain's reward regions. Among the many neuroadaptations that occur following repeated drug administration are alterations in cell morphology including changes in dendritic spines. While this phenomenon has been well documented, the underlying molecular mechanisms are poorly understood. Here, within the context of drug abuse, we review and integrate several of the established pathways known to regulate synaptic remodeling, and discuss the contributions of neurotrophic and dopamine signaling in mediating this structural plasticity. Finally, we discuss how such upstream mechanisms could regulate actin dynamics, the common endpoint involved in structural remodeling in neurons.
药物成瘾的特征是大脑奖赏区域存在持续的行为和细胞可塑性。反复给药后出现的众多神经适应性变化中,包括细胞形态的改变,如树突棘的变化。虽然这一现象已有充分记录,但其潜在的分子机制却知之甚少。在此,在药物滥用的背景下,我们回顾并整合了几种已知的调节突触重塑的既定途径,并讨论了神经营养信号和多巴胺信号在介导这种结构可塑性方面的作用。最后,我们讨论了这些上游机制如何调节肌动蛋白动力学,这是神经元结构重塑的共同终点。