Nestler Eric J
Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Sci Pract Perspect. 2005 Dec;3(1):4-10. doi: 10.1151/spp05314.
Cocaine produces its psychoactive and addictive effects primarily by acting on the brain's limbic system, a set of interconnected regions that regulate pleasure and motivation. An initial, short-term effect -- a buildup of the neurochemical dopamine -- gives rise to euphoria and a desire to take the drug again. Researchers are seeking to understand how cocaine's many longer term effects produce addiction's persistent cravings and risk of relapse. In the author's laboratory, work has focused on buildup of the genetic transcription factor DeltaFosB. Levels of DeltaFosB in the limbic system correlate with addiction-like behaviors in mice and may precipitate very long-lasting changes to nerve cell structure. Further pursuit of this and similar leads are first steps toward a complete understanding of the transition from cocaine abuse to addiction -- and, ultimately, more effective treatments for those who are addicted.
可卡因主要通过作用于大脑的边缘系统产生其精神活性和成瘾性作用,边缘系统是一组相互连接的区域,负责调节愉悦感和动机。最初的短期效应——神经化学物质多巴胺的积累——会产生欣快感,并使人渴望再次服用该药物。研究人员正在试图了解可卡因的许多长期效应是如何导致成瘾的持续渴望和复发风险的。在作者的实验室中,研究工作集中在基因转录因子DeltaFosB的积累上。边缘系统中DeltaFosB的水平与小鼠的成瘾样行为相关,并且可能促成神经细胞结构非常持久的变化。对这一及类似线索的进一步探究是全面理解从可卡因滥用转变为成瘾的第一步——最终,也是为成瘾者提供更有效治疗的第一步。