title: Predator odor stress alters corticotropin-releasing factor-1 receptor (CRF1R)-dependent behaviors in rats.
abstract: Humans with stress-related anxiety disorders exhibit increases in arousal and alcohol drinking, as well as altered pain processing. Our lab has developed a predator odor stress model that produces reliable and lasting increases in alcohol drinking. Here, we utilize this predator odor stress model to examine stress-induced increases in arousal, nociceptive processing, and alcohol self-administration by rats, and also to determine the effects of corticotropin-releasing factor-1 receptors (CRF1Rs) in mediating these behavioral changes. In a series of separate experiments, rats were exposed to predator odor stress, then tested over subsequent days for thermal nociception in the Hargreaves test, acoustic startle reactivity, or operant alcohol self-administration. In each experiment, rats were systemically injected with R121919, a CRF1R antagonist, and/or vehicle. Predator odor stress increased thermal nociception (i.e., hyperalgesia) and acoustic startle reactivity. Systemic administration of R121919 reduced thermal nociception and hyperarousal in stressed rats but not unstressed controls, and reduced operant alcohol responding over days. Stressed rats exhibited increased sensitivity to the behavioral effects of R121919 in all three tests, suggesting up-regulation of brain CRF1Rs number and/or function in stressed rats. These results suggest that post-stress alcohol drinking may be driven by a high-nociception high-arousal state, and that brain CRF1R signaling mediates these stress effects.
authors.affiliation: Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA, USA. Electronic address: eroltsch@lsuhsc.edu.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Roltsch
authors.affiliation: Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA, USA. Electronic address: bbayne@lsuhsc.edu.
authors.forename: Brittni B
authors.initials: BB
authors.lastname: Baynes
authors.affiliation: Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA, USA. Electronic address: jmaye2@lsuhsc.edu.
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Mayeux
authors.affiliation: Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA, USA. Electronic address: awhita@lsuhsc.edu.
authors.forename: Annie M
authors.initials: AM
authors.lastname: Whitaker
authors.affiliation: Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA, USA. Electronic address: bbaiam@lsuhsc.edu.
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Baiamonte
authors.affiliation: Department of Physiology, Louisiana State University Health Science Center, New Orleans, LA, USA. Electronic address: ngilpi@lsuhsc.edu.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Gilpin
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D003216:Conditioning, Operant; D004924:Escape Reaction / Q000187:drug effects* / Q000502:physiology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009812:Odorants; D055696:Olfactory Perception / Q000187:drug effects / Q000502:physiology; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000188:drug therapy* / Q000503:physiopathology*; D000099052:CRF Receptor, Type 1
chemical_list: D011743:Pyrimidines; C412383:R 121919; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1
keywords: Alcohol use disorder; CRF; CRF1R; Escalation; Hargreaves; Hyperalgesia; Hyperarousal; Operant; Predator odor; Self-administration; Startle; Stress