Differential c-Fos Response in Neurocircuits Activated by Repeated Predator Stress in Male and Female C57BL/6J Mice with Stress Sensitive or Resilient Alcohol Intake Phenotypes

Predator odor stress reactivity, alcohol drinking and the endocannabinoid system

“…This is an important finding as it suggests male mice with greater sensitivity (i.e. increased alcohol drinking) to repeated predator odor stress have increased HPA axis activity, suggestive of greater stressor response and potentially indicative of a maladaptive neuroendocrine response to stress ( Clark et al, 2023 ). Furthermore, Alavi et al (2022) showed that in the PFC, CRF receptor 1,2, binding protein and GR were higher in female mice in the sensitive subgroup, but this was not found in males.…”

“…For example, Clark et al (2021) examined c-Fos activation between sensitive and resilient phenotypes in male and female mice after repeated exposure to dirty rat bedding. Male mice in the sensitive subgroup demonstrated higher c-Fos induction in the paraventricular nucleus of the hypothalamus (PVH) and piriform cortex (Pir) ( Clark et al, 2023 ). This is an important finding as it suggests male mice with greater sensitivity (i.e.…”

“…Another predator odor stressor that has been extensively used in mice, is exposure to dirty rat bedding ( Alavi et al, 2022 ; Finn et al, 2018 ; Cozzoli et al, 2014 ; Devaud et al, 2020 ; Manjoch et al, 2016 ; Clark et al, 2023 ; Nipper et al, 2024 ). This model has been used to study sex differences in response to stress, increases in ethanol intake after stressor exposure and neurochemical changes induced by predator odor stress.…”

Nucleus accumbens shell cholinergic interneurons potently drive binge alcohol drinking: A commentary on Sharma et al., 2024

“…In addition, there are no sex differences in changes in NAcSh cholinergic markers in response to adolescent alcohol exposure (Hauser et al., 2021), or in ventral tegmental area GABA projections onto NAcSh CINs (Al‐Hasani et al., 2021). There are also no sex differences in how adolescent alcohol increases pain and NAcSh signaling (Kelley et al., 2023), or in stress response activation of NAcSh neurons (Clark et al., 2023). Thus, one possibility is that multiple drivers of motivated behavior converge in NAcSh, but that mechanisms that promote higher female alcohol drinking, and often greater punishment‐resistant drinking (Radke et al., 2021), are downstream of NAcSh.…”