Predator odor stress alters corticotropin-releasing factor-1 receptor (CRF1R)-dependent behaviors in rats

Roltsch, Emily; Baynes, Brittni B; Mayeux, Jacques P.; Whitaker, Annie M.; Baiamonte, Brandon A.; Gilpin, Nicholas W.

doi:10.1016/j.neuropharm.2013.11.005

Cited by 40 publications

(36 citation statements)

References 82 publications

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“…These data suggest that predator odor is a powerful aversive stimulus that produces similar increases in anxiety-like behavior in all stressed rats. This is in agreement with previous reports that predator odor increases anxiety-like behavior (1, 5) and startle reactivity in rats (1, 22). Other types of stress (e.g., restraint stress or footshock) also produce increases in anxiety-like behavior as measured by the EPM and open field test (3, 13).…”

Section: Discussionsupporting

confidence: 94%

Blunted hypothalamo-pituitary adrenal axis response to predator odor predicts high stress reactivity

Whitaker

Gilpin

2015

Physiology & Behavior

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Individuals with trauma- and stress-related disorders exhibit increases in avoidance of trauma-related stimuli, heightened anxiety and altered neuroendocrine stress responses. Our laboratory uses a rodent model of stress that mimics the avoidance symptom cluster associated with stress-related disorders. Animals are classified as ‘Avoiders’ or Non-Avoiders' post-stress based on avoidance of predator-odor paired context. Utilizing this model, we are able to examine subpopulation differences in stress reactivity. Here, we used this predator odor model of stress to examine differences in anxiety-like behavior and hypothalamo-pituitary adrenal (HPA) axis function in animals that avoid a predator-paired context relative to those that do not. Rats were exposed to predator odor stress paired with a context and tested for avoidance (24 hours and 11 days), anxiety-like behavior (48 hours and 5 days) and HPA activation following stress. Control animals were exposed to room air. Predator odor stress produced avoidance in approximately 65% of the animals at 24 hours that persisted 11 days post-stress. Both Avoiders and Non-Avoiders exhibited heightened anxiety-like behavior at 48 hours and 5 days post-stress when compared to unstressed Controls. Non-Avoiders exhibited significant increases in circulating adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations immediately following predator odor stress compared to Controls and this response was significantly attenuated in Avoiders. There was an inverse correlation between circulating ACTH/CORT concentrations and avoidance, indicating that lower levels of ACTH/CORT predicted higher levels of avoidance. These results suggest that stress effects on HPA stress axis activation predict long-term avoidance of stress-paired stimuli, and builds on previous data showing the utility of this model for exploring the neurobiological mechanisms of trauma- and stress-related disorders.

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Section: Discussionsupporting

confidence: 94%

Blunted hypothalamo-pituitary adrenal axis response to predator odor predicts high stress reactivity

Whitaker

Gilpin

2015

Physiology & Behavior

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“…In agreement with the current results that predator odor stress using dirty rat bedding increased subsequent ethanol consumption in male and female C57BL/6J mice, male Wistar rats increased operant responding for ethanol after exposure to predator odor stress using bobcat urine (at least in those animals which avoided the odor-paired chamber; Edwards et al, 2013; Roltsch et al, 2014). Exposure to bobcat urine also increased thermal nociception 5 days later and increased startle reactivity 2 days later (Roltsch et al, 2014), suggesting that a high arousal and high nociception state after predator odor stress may contribute to the increase in ethanol self-administration. Mice also exhibit increased anxiety after exposure to predator odor stress.…”

Section: Discussionsupporting

confidence: 92%

“…In support of this general hypothesis, limited available data in other genotypes indicate that repeated restraint stress significantly increased ethanol intake in male and significantly decreased ethanol intake in female mice that were selectively bred for high alcohol preference (HAP; Chester et al, 2006), and that tail suspension stress significantly increased ethanol intake only in female but not in male CD-1 mice with high immobility scores (Pelloux et al, 2005). Finally, because perceived predation risk has a profound biological effect across species (Zanette et al, 2011), and predator odor stress significantly increased ethanol self-administration in male Wistar rats (Edwards et al, 2013; Roltsch et al, 2014), we predicted that exposure to predator odor stress would significantly increase ethanol intake and that the effect might be more pronounced in female mice.…”

Section: Introductionmentioning

confidence: 99%

Environmental stressors influence limited-access ethanol consumption by C57BL/6J mice in a sex-dependent manner

Cozzoli

Tanchuck-Nipper

Kaufman

et al. 2014

Alcohol

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Environmental factors, including exposure to stress, are known to contribute to the propensity to consume ethanol. However, stress produces inconsistent effects on ethanol drinking in rodent models. Therefore, the present study examined the impact of different stressors on limited access ethanol consumption and determined whether there were sex-dependent differences in response to stress. To this end, male and female C57BL/6J mice had 2-hr access to a water and 10% ethanol solution, beginning 30 minutes before onset of the dark cycle. Once ethanol intake was stable, the effect of restraint, tail suspension, predator odor, foot shock, and tail pinch on subsequent intake was explored. Both plasma corticosterone (CORT) and allopregnanolone (ALLO) were assessed as indices of hypothalamic-pituitary-adrenal (HPA) axis activity and of endogenous neurosteroid levels respectively, following restraint, tail suspension and predator odor. Ethanol intake was decreased following restraint, tail suspension, foot shock, and tail pinch in both sexes, with stressor-related differences in the duration of the suppression. The effect of predator odor on ethanol intake was biphasic in females; ethanol consumption was significantly reduced on the day of stress but significantly increased on the following two days. In males, predator odor produced a delayed significant increase in ethanol intake on the second day after stress. All three stressors increased plasma CORT, with higher CORT levels in females when compared with males. Notably, there was a significant positive correlation between CORT levels immediately after predator odor stress and ethanol intake on the following day as well as a significant positive linear relationship between CORT levels immediately after restraint stress and ethanol intake on the following day in females. Furthermore, the three stressors produced a greater increase in ALLO levels in female versus male mice, but ALLO levels following predator odor were not correlated with subsequent ethanol intake. In summary, the type of stressor administered had a profound impact on subsequent ethanol consumption, with subtle sex differences in the magnitude and persistence of the effect. These findings are the first to demonstrate that a single, acute exposure to restraint, tail suspension, and predator odor stress increased plasma CORT and ALLO levels in animals with a history of ethanol consumption and that female mice were more responsive than males to the ability of stress to increase CORT levels as well as to the ability of predator odor stress to produce a delayed increase in ethanol intake. Because predator odor stress is a model of posttraumatic stress disorder, the present sex differences have important implications for future preclinical studies modeling the comorbidity of posttraumatic stress disorder and alcohol use disorders.

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“…With respect to nociception, both stress and intraCeA corticosterone pellet implants produce somatic hypersensitivity by increasing CRF expression in CeA, and these effects are blocked by antisense CRF knockdown in CeA (Johnson et al, 2015). Previous work by our group showed that predator odor exposure increases thermal nociception and this effect is reversed by systemic blockade of CRFR1s (Roltsch et al, 2014).…”

Section: Introductionmentioning

confidence: 86%

Traumatic Stress Promotes Hyperalgesia via Corticotropin-Releasing Factor-1 Receptor (CRFR1) Signaling in Central Amygdala

Itoga

Hellard

Whitaker

et al. 2016

Neuropsychopharmacol

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Hyperalgesia is an exaggerated response to noxious stimuli produced by peripheral or central plasticity. Stress modifies nociception, and humans with post-traumatic stress disorder (PTSD) exhibit co-morbid chronic pain and amygdala dysregulation. Predator odor stress produces hyperalgesia in rodents. Systemic blockade of corticotropin-releasing factor (CRF) type 1 receptors (CRFR1s) reduces stressinduced thermal hyperalgesia. We hypothesized that CRF-CRFR1 signaling in central amygdala (CeA) mediates stress-induced hyperalgesia in rats with high stress reactivity. Adult male Wistar rats were exposed to predator odor stress in a conditioned place avoidance paradigm and indexed for high (Avoiders) and low (Non-Avoiders) avoidance of predator odor-paired context, or were unstressed Controls. Rats were tested for the latency to withdraw hindpaws from thermal stimuli (Hargreaves test). We used pharmacological, molecular, and immunohistochemical techniques to assess the role of CRF-CRFR1 signaling in CeA in stress-induced hyperalgesia. Avoiders exhibited higher CRF peptide levels in CeA that did not appear to be locally synthesized. Intra-CeA CRF infusion mimicked stress-induced hyperalgesia. Avoiders exhibited thermal hyperalgesia that was reversed by systemic or intra-CeA injection of a CRFR1 antagonist. Finally, intra-CeA infusion of tetrodotoxin produced thermal hyperalgesia in unstressed rats and blocked the anti-hyperalgesic effect of systemic CRFR1 antagonist in stressed rats. These data suggest that rats with high stress reactivity exhibit hyperalgesia that is mediated by CRF-CRFR1 signaling in CeA.

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Predator odor stress alters corticotropin-releasing factor-1 receptor (CRF1R)-dependent behaviors in rats

Cited by 40 publications

References 82 publications

Blunted hypothalamo-pituitary adrenal axis response to predator odor predicts high stress reactivity

Blunted hypothalamo-pituitary adrenal axis response to predator odor predicts high stress reactivity

Environmental stressors influence limited-access ethanol consumption by C57BL/6J mice in a sex-dependent manner

Traumatic Stress Promotes Hyperalgesia via Corticotropin-Releasing Factor-1 Receptor (CRFR1) Signaling in Central Amygdala

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