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bioRxiv · 10.1101/870386

THE ROLE OF CENTRAL AMYGDALA CORTICOTROPIN-RELEASING FACTOR IN PREDATOR ODOR STRESS-INDUCED AVOIDANCE BEHAVIOR AND ESCALATED ALCOHOL DRINKING IN RATS

Weera, M. M.·Schreiber, A. L.·Avegno, E. M.·Gilpin, N. W.
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Abstract

Post-traumatic stress disorder (PTSD) is characterized by avoidance of trauma-associated stimuli and amygdala hyperreactivity, and is highly co-morbid with alcohol use disorder (AUD). Our lab uses a predator odor (bobcat urine) stress model that produces conditioned avoidance of an odor-paired context in a subset of rats, mirroring avoidance symptoms that manifest in some but not all humans exposed to trauma. We previously showed that after predator odor stress, Avoiders exhibit escalated alcohol drinking, higher aversion-resistant operant alcohol responding, hyperalgesia, and greater anxiety-like behavior compared to unstressed Controls. We also showed that systemic antagonism of corticotropin-releasing factor-1 receptors (CRFR1) reduced escalation of alcohol drinking in rats not indexed for avoidance, that corticotropin-releasing factor (CRF) infusions into the central amygdala (CeA) produced conditioned place avoidance in stress-naive rats, and that intra-CeA infusion of a CRFR1 antagonist reduced hyperalgesia in Avoiders. Here, we show that avoidance behavior is persistent after repeated predator odor exposure and is resistant to extinction. In addition, Avoiders showed lower weight gain than Controls after predator odor re-exposure. In the brain, higher avoidance was correlated with higher number of c-Fos+ cells and CRF immunoreactivity in the CeA. Finally, we show that intra-CeA CRFR1 antagonism reversed post-stress escalation of alcohol drinking and reduced avoidance behavior in Avoiders. Collectively, these findings suggest that elucidation of the mechanisms by which CRFR1-gated CeA circuits regulate avoidance behavior and alcohol drinking may lead to better understanding of the neural mechanisms underlying co-morbid PTSD and AUD.

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Weera, M. M., Schreiber, A. L., Avegno, E. M., Gilpin, N. W.. 2019-12-10. THE ROLE OF CENTRAL AMYGDALA CORTICOTROPIN-RELEASING FACTOR IN PREDATOR ODOR STRESS-INDUCED AVOIDANCE BEHAVIOR AND ESCALATED ALCOHOL DRINKING IN RATS. https://doi.org/10.1101/870386

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