Vargas-Perez Hector, Ting-A Kee Ryan, Walton Christine H, Hansen D Micah, Razavi Rozita, Clarke Laura, Bufalino Mary Rose, Allison David W, Steffensen Scott C, van der Kooy Derek
Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
Science. 2009 Jun 26;324(5935):1732-4. doi: 10.1126/science.1168501. Epub 2009 May 28.
The neural mechanisms underlying the transition from a drug-nondependent to a drug-dependent state remain elusive. Chronic exposure to drugs has been shown to increase brain-derived neurotrophic factor (BDNF) levels in ventral tegmental area (VTA) neurons. BDNF infusions into the VTA potentiate several behavioral effects of drugs, including psychomotor sensitization and cue-induced drug seeking. We found that a single infusion of BDNF into the VTA promotes a shift from a dopamine-independent to a dopamine-dependent opiate reward system, identical to that seen when an opiate-naïve rat becomes dependent and withdrawn. This shift involves a switch in the gamma-aminobutyric acid type A (GABAA) receptors of VTA GABAergic neurons, from inhibitory to excitatory signaling.
从药物非依赖状态转变为药物依赖状态的神经机制仍然难以捉摸。长期接触药物已被证明会增加腹侧被盖区（VTA）神经元中脑源性神经营养因子（BDNF）的水平。向VTA中注入BDNF会增强药物的几种行为效应，包括精神运动性敏感化和线索诱导的觅药行为。我们发现，向VTA中单次注入BDNF会促进从多巴胺非依赖性阿片奖赏系统向多巴胺依赖性阿片奖赏系统的转变，这与从未接触过阿片类药物的大鼠产生依赖性并戒断时的情况相同。这种转变涉及VTA中γ-氨基丁酸A型（GABAA）受体从抑制性信号向兴奋性信号的转换。
