Increased mGlu5 mRNA expression in BLA glutamate neurons facilitates resilience to the long-term effects of a single predator scent stress exposure

Shallcross, John; Wu, Lizhen; Wilkinson, Courtney; Knackstedt, Lori A.; Schwendt, Marek

doi:10.1007/s00429-021-02326-4

Cited by 11 publications

(14 citation statements)

References 77 publications

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“…Metabotropic glutamate receptor 5 (mGlu5) has been implicated in mediating resilience to stress-induced anhedonia and anxiety in rodents (28–32). In agreement with those works, we have found that male rats “resilient” to the long-term effects of predator scent stress (PSS) exhibit greater PFC and BLA mGlu5 mRNA expression, and mGlu5 antagonists and agonists bidirectionally alter contextual fear in this model (31,33–37).…”

Section: Introductionsupporting

confidence: 91%

“…We next compared time spent in the OA, sucrose intake, and mean ASR between Susceptible, Resilient and Control rats. There was a significant effect of Phenotype for time spent in the OA [F(2, 33) = 15.03, p<0.0001; Fig. 2C].…”

Section: Resultsmentioning

confidence: 99%

“…Post-hoc tests showed that Susceptible rats spent less time in the OA than both Control and Resilient rats (p’s <0.05). For total sucrose consumed (mL), there was a significant effect of Phenotype [F(2, 33) = 16.34, p<0.0001, Fig. 2D].…”

Section: Resultsmentioning

confidence: 99%

“…Time spent in the dark compartment of the light-dark box differed by Phenotype [F (2, 33) = 8.323, p = 0.0012, Fig. 3A].…”

Section: Resultsmentioning

confidence: 99%

“…Signal was artificially boosted using Speckles enhancement. Only mRNA masked within DAPI- and vGluT1-positive neurons were reported for statistical purposes (33).…”

Section: Methodsmentioning

confidence: 99%

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Resilience to anxiety and anhedonia after predator scent stress is accompanied by increased nucleus accumbens mGlu5 in female rats

Blount

Dee

et al. 2022

Preprint

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Despite the higher prevalence of post-traumatic stress disorder (PTSD) in women, the majority of preclinical neuroscience 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 development of 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. Here we sought to determine whether the same behavioral and genetic responses would be observed in female rats exposed to TMT. 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 (ASR), light/dark box, and sucrose preference test. TMT-exposed females spent less time in the EPM open arms and exhibited greater startle amplitude, and reduced sucrose intake compared to Controls. Median split analyses conducted on EPM and sucrose intake yielded phenotypes that displayed behavior in the light/dark box consistent with EPM and sucrose testing. Unlike male Susceptible rats, female Susceptible rats showed no freezing when re-exposed to the TMT context, nor did Resilient female rats present elevated BLA mGlu5 mRNA levels. Instead, Susceptible females had greater BLA mGlu5 than Resilient or Control rats. This work indicates that, as in humans, rats exhibit sex-dependent responses to stress. This translational animal model may provide insight into how females are uniquely affected by PTSD.

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Section: Introductionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Time spent in the dark compartment of the light-dark box differed by Phenotype [F (2, 33) = 8.323, p = 0.0012, Fig. 3A].…”

Section: Resultsmentioning

confidence: 99%

“…Signal was artificially boosted using Speckles enhancement. Only mRNA masked within DAPI- and vGluT1-positive neurons were reported for statistical purposes (33).…”

Section: Methodsmentioning

confidence: 99%

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