Accelerated development of cocaine-associated dopamine transients and cocaine use vulnerability following traumatic stress
Accelerated development of cocaine-associated dopamine transients and cocaine use vulnerability following traumatic stress
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DOI：
10.1038/s41386-019-0526-1
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发表时间：
2020-02-01
影响因子：
7.6
通讯作者：
Espana, Rodrigo A.
中科院分区：
文献类型：
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作者：
Brodnik, Zachary D.;Black, Emily M.;Espana, Rodrigo A.
创伤后应激障碍和可卡因使用障碍是高度共病的精神疾病。创伤后应激障碍的发病通常早于可卡因使用障碍的发展，因此创伤后应激障碍的发展似乎驱动了可卡因使用脆弱性。我们最近描述了一个创伤后应激障碍大鼠模型，基于高水平迷宫和情境回避中的焦虑样行为，将大鼠分为易感和弹性。我们将该模型与自由运动大鼠体内快速扫描循环伏安法配对，以测试基线时伏隔核核心多巴胺信号的差异，对单剂量可卡因的反应，以及对可卡因配对线索的反应。此外，我们还研究了各组间获得可卡因自我给药的差异。结果表明，对创伤应激的易感性与相多巴胺信号结构的改变有关，这种改变增加了多巴胺信号携带可卡因相关线索的速率，并增加了训练后持续线索诱发的多巴胺信号的强度。这些阶段性多巴胺信号的变化与易感大鼠产生过量吸食可卡因行为的速率增加相对应。总之，我们的研究表明，对创伤应激的易感性与可卡因使用易感性表型有关，并表明相多巴胺信号结构的差异可能有助于这种易感性发生的过程。
Post-traumatic stress disorder and cocaine use disorder are highly co-morbid psychiatric conditions. The onset of post-traumatic stress disorder generally occurs prior to the development of cocaine use disorder, and thus it appears that the development of post-traumatic stress disorder drives cocaine use vulnerability. We recently characterized a rat model of post-traumatic stress disorder with segregation of rats as susceptible and resilient based on anxiety-like behavior in the elevated plus maze and context avoidance. We paired this model with in vivo fast scan cyclic voltammetry in freely moving rats to test for differences in dopamine signaling in the nucleus accumbens core at baseline, in response to a single dose of cocaine, and in response to cocaine-paired cues. Further, we examined differences in the acquisition of cocaine self-administration across groups. Results indicate that susceptibility to traumatic stress is associated with alterations in phasic dopamine signaling architecture that increase the rate at which dopamine signals entrain to cocaine-associated cues and increase the magnitude of persistent cue-evoked dopamine signals following training. These changes in phasic dopamine signaling correspond with increases in the rate at which susceptible rats develop excessive cocaine-taking behavior. Together, our studies demonstrate that susceptibility to traumatic stress is associated with a cocaine use-vulnerable phenotype and suggests that differences in phasic dopamine signaling architecture may contribute to the process by which this vulnerability occurs.