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Neuropharmacology. 2017 Feb;113(Pt A):323-330. doi: 10.1016/j.neuropharm.2016.05.008. Epub 2016 May 24.

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

Author information

1
Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
2
Neuroscience and Behavior Program, University of Massachusetts, Amherst, MA, 01003, USA.
3
Department of Psychological and Brain Sciences, University of Massachusetts, Amherst, MA, 01003, USA.
4
Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA 70112, USA; Neuroscience Center of Excellence, Louisiana State University Health Science Center, New Orleans, LA, 70112, USA. Electronic address: ngilpi@lsuhsc.edu.

Abstract

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.

KEYWORDS:

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

PMID:
27235163
PMCID:
PMC5122468
DOI:
10.1016/j.neuropharm.2016.05.008
[Indexed for MEDLINE]
Free PMC Article

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