Stress resilience-associated behaviors following predator scent stress are accompanied by upregulated nucleus accumbens mGlu5 transcription in female Sprague Dawley rats

Abstract

Despite the higher prevalence of post-traumatic stress disorder (PTSD) in women, the majority of preclinical research has been conducted utilizing male subjects. We have found that male rats exposed to the predator scent 2,4,5-trimethyl-3-thiazoline (TMT) show heterogenous long-term anxiety-like behavior and conditioned fear to the TMT environment. Stress-Resilient males exhibit increased mGlu5 mRNA expression in the basolateral amygdala (BLA) and prefrontal cortex (PFC). Here we sought to determine whether the same behavioral and genetic responses would be observed in female rats exposed to TMT. Female Sprague-Dawley rats were exposed to TMT for ten minutes, while Controls were exposed to an unscented environment. Anxiety and anhedonia were assessed 7-14 days later with elevated plus maze (EPM), acoustic startle response, light-dark box, and sucrose preference test (SPT). TMT-exposed females spent less time in the EPM open arms, exhibited greater startle amplitude, and reduced sucrose intake compared to Controls. Median split analyses conducted on EPM and SPT data yielded stress-Susceptible and -Resilient phenotypes that displayed behavior in the light-dark box consistent with EPM and SPT behavior. Susceptible females displayed greater BLA mGlu5 mRNA expression than Resilient and Control rats and did not show conditioned fear, in contrast to previous results in males. Resilient females displayed greater mGlu5 mRNA expression in the nucleus accumbens. These data indicate that the predator scent stress model of PTSD produces distinct stress-Susceptible and Resilient phenotypes in female rats that are associated with changes in mGlu5 mRNA expression in several brain regions.

Keywords: Anhedonia; Anxiety; Glutamate; Nucleus reuniens; Predator odor; TMT.