Corticotropin-releasing factor in ventromedial prefrontal cortex mediates avoidance of a traumatic stress-paired context

NEUROPHARMACOLOGY

卷:113

Article

Schreiber, Allyson L.¹  Lu, Yi-Ling²  Baynes, Brittni B.¹  Richardson, Heather N.³  Gilpin, Nicholas W.^1,4 

[1] Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70112 USA

[2] Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA

[3] Univ Massachusetts, Dept Psychol & Brain Sci, Amherst, MA 01003 USA

[4] Louisiana State Univ, Hlth Sci Ctr, Neurosci Ctr Excellence, New Orleans, LA 70112 USA

关键词: Post-traumatic stress disorder (PTSD);    Avoidance;    Alcohol self-administration;    Medial prefrontal cortex (mPFC);    Corticotropin-releasing factor (CRF);    Anxiety;   

DOI  :  10.1016/j.neuropharm.2016.05.008

来源: Elsevier

【 摘 要 】

Post-traumatic stress disorder (PTSD) affects 7.7 million Americans. One diagnostic criterion for PTSD is avoidance of stimuli that are related to the traumatic stress. Using a predator odor stress conditioned place aversion (CPA) model, rats can be divided into groups based on stress reactivity, as measured by avoidance of the odor-paired context. Avoider rats, which show high stress reactivity, exhibit persistent avoidance of stress-paired context and escalated alcohol drinking. Here, we examined the potential role of corticotropin-releasing factor (CRF), a neuropeptide that promotes anxiety-like behavior in mediating avoidance and escalated alcohol drinking after stress. CRF is expressed in the medial prefrontal cortex (mPFC). The dorsal and ventral sub-regions of the mPFC (dmPFC and vmPFC) have opposing roles in stress reactivity and alcohol drinking. We hypothesized that vmPFC CRF-CRFR1 signaling contributes functionally 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. Post-stress, Avoiders exhibited higher CRF cell density in vmPFC, but not the 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 and indexed, then tested for the effects of intra-vmPFC CRFR1 antagonism on avoidance and alcohol self-administration. Intra-vmPFC CRF infusion produced avoidance of a paired context, and intra-vmPFC CRFR1 antagonism reversed avoidance of a stress-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. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

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