Corticotropin-releasing factor in ventromedial prefrontal cortex mediates avoidance of a traumatic stress-paired context.
Corticotropin-releasing factor in ventromedial prefrontal cortex mediates avoidance of a traumatic stress-paired context.
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DOI：
10.1016/j.neuropharm.2016.05.008
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发表时间：
2017-02
影响因子：
4.7
通讯作者：
Gilpin NW
中科院分区：
文献类型：
--
作者：
Schreiber AL;Lu YL;Baynes BB;Richardson HN;Gilpin NW
创伤后应激障碍影响着770万美国人。一个诊断标准是避免与创伤应激相关的刺激。利用捕食者气味应激条件位置回避(CPA)模型，可以根据应激反应将大鼠分成不同的组，通过回避气味配对的环境来衡量。回避大鼠表现出高度的应激反应，表现出对压力配对环境的回避和不断增加的饮酒。在这里，我们研究了促肾上腺皮质激素释放因子(CRF)在调节压力后回避和酗酒升级中的作用，CRF是一种促进焦虑样行为的神经肽。CRF在内侧前额叶皮质(MPFC)表达。MPFC的背侧和腹侧亚区(dmPFC和vmPFC)在应激反应和饮酒/寻求中具有相反的作用。我们假设vmPFC中的CRF-CRFR1信号有助于压力诱导的回避和升级的酒精自我给药。在实验1中，成年雄性Wistar大鼠在CPA范式下暴露于捕食者气味应激，为避免气味配对环境而进行索引，并在vmPFC和dmPFC中处理大脑中CRF免疫反应细胞密度。在实验2中，大鼠被测试避免与vmPFC内注射CRF重复配对的上下文。在实验3中，对大鼠进行应激、指标化，并测试vmPFC CRFR1拮抗对回避和酒精自我给药的影响。应激后，回避组大鼠vmPFC的CRF细胞密度较高，而dmPFC组无明显变化。VmPFC内输注CRF产生条件性位置回避。VmPFC CRFR1内拮抗逆转了对气味环境的回避，但不改变应激后酒精自我给药。这些发现表明，vmPFC、CRF-CRFR1信号介导了创伤应激对刺激的回避。
Post-traumatic stress disorder affects 7.7 million Americans. One diagnostic criterion is avoidance of stimuli related to the traumatic stress. Using a predator odor stress conditioned place avoidance (CPA) model, rats can be divided into groups based on stress reactivity, measured by avoidance of the odor-paired context. Avoider rats, which show high stress reactivity, exhibit avoidance of stress-paired context and escalated alcohol drinking. Here, we examined the role of corticotropin-releasing factor (CRF), a neuropeptide that promotes anxiety-like behavior, in mediating post-stress avoidance and escalated alcohol drinking. CRF is expressed in the medial prefrontal cortex (mPFC). The dorsal and ventral sub-regions of mPFC (dmPFC and vmPFC) have opposing roles in stress reactivity and alcohol drinking/seeking. We hypothesized that CRF-CRFR1 signaling in the vmPFC contributes to stress-induced avoidance and escalated alcohol self-administration. In Experiment 1, adult male Wistar rats were exposed to predator odor stress in a CPA paradigm, indexed for avoidance of odor-paired context, and brains processed for CRF-immunoreactive cell density in vmPFC and dmPFC. In Experiment 2, rats were tested for avoidance of a context repeatedly paired with intra-vmPFC CRF infusions. In Experiment 3, rats were stressed, indexed, and tested for the effects of intra-vmPFC CRFR1 antagonism on avoidance and alcohol self-administration. Post-stress, Avoiders exhibited higher CRF cell density in vmPFC, but not dmPFC. Intra-vmPFC CRF infusion produced conditioned place avoidance. Intra-vmPFC CRFR1 antagonism reversed avoidance of odor-paired context, but did not alter post-stress alcohol self-administration. These findings suggest that vmPFC CRF-CRFR1 signaling mediates avoidance of stimuli paired with traumatic stress.
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影响因子：
3.3
作者：
Karanikas, C. A.;Lu, Y-L;Richardson, H. N.
通讯作者：
Richardson, H. N.
影响因子：
8.2
作者：
George, Olivier;Koob, George F.
通讯作者：
Koob, George F.
影响因子：
3.6
作者：
Motzkin, Julian C.;Philippi, Carissa L.;Oler, Jonathan A.;Kahn, Ned H.;Baskaya, Mustafa K.;Koenigs, Michael
通讯作者：
Koenigs, Michael
影响因子：
10.6
作者：
Motzkin, Julian C.;Philippi, Carissa L.;Wolf, Richard C.;Baskaya, Mustafa K.;Koenigs, Michael
通讯作者：
Koenigs, Michael
影响因子：
2.9
作者：
CADOR, M;AHMED, SH;STINUS, L
通讯作者：
STINUS, L