Miguel-Hidalgo Jose Javier
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Curr Drug Abuse Rev. 2009 Jan;2(1):72-82.
Neuronal dysfunction in the prefrontal cortex, limbic structures, nucleus accumbens and ventral tegmental area is considered to underlie the general physiopathological mechanisms for substance use disorders. Glutamatergic, dopaminergic and opioidoergic neuronal mechanisms in those brain areas have been targeted in the development of pharmacotherapies for drug abuse and dependence. However, despite the pivotal role of neurons in the mechanisms of addiction, these cells are not the only cell type in charge of sustaining and regulating neurotransmission. Glial cells, particularly astrocytes, play essential roles in the regulation of glutamatergic neurotransmission, neurotransmitter metabolism, and supply of energy substrates for synaptic transmission. In addition, astrocytes are markedly affected by exposure to ethanol and other substances of abuse. These features of astrocytes suggest that alterations in the function of astrocytes and other glial cells in reward circuits may contribute to drug addiction. Recent research has shown that the control of glutamate uptake and the release of neurotrophic factors by astrocytes influences behaviors of addiction and may play modulatory roles in psychostimulant, opiate, and alcohol abuse. Less is known about the contributions of microglia and oligodendrocytes to drug abuse, although, given the ability of these cells to produce growth factors and cytokines in response to alterations in synaptic transmission, further research should better define their role in drug addiction. The available knowledge on the involvement of glial cells in addictive behaviors suggests that regulation of glutamate transport and neurotrophins may constitute new avenues for the treatment of drug addiction.
前额叶皮质、边缘系统结构、伏隔核和腹侧被盖区的神经元功能障碍被认为是物质使用障碍的一般生理病理机制的基础。这些脑区的谷氨酸能、多巴胺能和阿片样物质能神经元机制已成为药物滥用和依赖药物治疗开发的靶点。然而，尽管神经元在成瘾机制中起关键作用，但这些细胞并不是负责维持和调节神经传递的唯一细胞类型。神经胶质细胞，尤其是星形胶质细胞，在谷氨酸能神经传递的调节、神经递质代谢以及为突触传递提供能量底物方面发挥着重要作用。此外，星形胶质细胞受到乙醇和其他滥用物质的显著影响。星形胶质细胞的这些特征表明，奖赏回路中星形胶质细胞和其他神经胶质细胞功能的改变可能导致药物成瘾。最近的研究表明，星形胶质细胞对谷氨酸摄取的控制和神经营养因子的释放会影响成瘾行为，并且可能在精神兴奋剂、阿片类药物和酒精滥用中起调节作用。关于小胶质细胞和少突胶质细胞对药物滥用的作用了解较少，不过，鉴于这些细胞能够响应突触传递的改变而产生生长因子和细胞因子，进一步的研究应该能更好地确定它们在药物成瘾中的作用。关于神经胶质细胞参与成瘾行为的现有知识表明，调节谷氨酸转运和神经营养因子可能构成治疗药物成瘾的新途径。
