Cocaine experience establishes control of midbrain glutamate and dopamine by corticotropin-releasing factor: A role in stress-induced relapse to drug seeking
Cocaine experience establishes control of midbrain glutamate and dopamine by corticotropin-releasing factor: A role in stress-induced relapse to drug seeking
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DOI：
10.1523/jneurosci.0955-05.2005
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发表时间：
2005-06-01
影响因子：
5.3
通讯作者：
You, ZB
中科院分区：
文献类型：
--
作者：
Wang, B;Shaham, Y;You, ZB
足电击应激可以通过应激相关神经激素促肾上腺皮质激素释放因子（CRF）的中枢作用恢复可卡因寻求行为。在这里，我们报告（1）足电击应激释放大鼠大脑腹侧被盖区（VTA）的CRF，（2）在可卡因经验丰富的大鼠中，而不是在可卡因未处理的大鼠中，CRF获得对局部谷氨酸释放的控制，（3）CRF诱导的谷氨酸释放激活中皮质边缘多巴胺系统，（4）通过这一回路，足电击应激触发可卡因经验动物的药物寻求复发。因此，一个持久的可卡因诱导的神经适应，大概在腹侧被盖区的谷氨酸终端的水平，似乎发挥了重要作用，在压力诱导的复发药物使用。类似的神经适应对于成瘾和其他压力相关精神疾病之间的共病可能很重要。
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.