Wang Bin, Shaham Yavin, Zitzman Dawnya, Azari Soraya, Wise Roy A, You Zhi-Bing
Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
J Neurosci. 2005 Jun 1;25(22):5389-96. doi: 10.1523/JNEUROSCI.0955-05.2005.
Footshock stress can reinstate cocaine-seeking behavior through a central action of the stress-associated neurohormone corticotropin-releasing factor (CRF). Here we report (1) that footshock stress releases CRF in the ventral tegmental area (VTA) of the rat brain, (2) that, in cocaine-experienced but not in cocaine-naive rats, this CRF acquires control over local glutamate release, (3) that CRF-induced glutamate release activates the mesocorticolimbic dopamine system, and (4) that, through this circuitry, footshock stress triggers relapse to drug seeking in cocaine-experienced animals. Thus, a long-lasting cocaine-induced neuroadaptation, presumably at the level of glutamate terminals in the VTA, appears to play an important role in stress-induced relapse to drug use. Similar neuroadaptations may be important for the comorbidity between addiction and other stress-related psychiatric disorders.
足部电击应激可通过应激相关神经激素促肾上腺皮质激素释放因子（CRF）的中枢作用恢复觅可卡因行为。在此我们报告：（1）足部电击应激可使大鼠脑腹侧被盖区（VTA）释放CRF；（2）在有可卡因使用经历的大鼠而非无此经历的大鼠中，这种CRF可控制局部谷氨酸释放；（3）CRF诱导的谷氨酸释放可激活中脑皮质边缘多巴胺系统；（4）通过这一神经环路，足部电击应激可触发有可卡因使用经历动物的复吸行为。因此，可卡因诱导的一种持久的神经适应性变化，可能发生在VTA谷氨酸能终末水平，似乎在应激诱导的药物复吸中起重要作用。类似的神经适应性变化可能对成瘾与其他应激相关精神障碍之间的共病现象具有重要意义。
