Sial & Allsop

Sial et al. derived a novel approach for studying what they deem vicarious defeat stress (VSDS) as a model for MDD, PTSD, and other mood-related disorders as an alternative to the classical CSDS paradigm. Using adult male mice, they demonstrate that their model induces a robust and measurable social avoidant phenotype as well as other stress and anxiety related behavioral outputs. Their subsequent rescue study with chronic fluoxetine treatment shows reversal of the behavioral phenotypes and emphasizes the predictive validity of the model. Allsop et al. found that BLA-projecting ACC neurons preferentially encode socially derived aversive cue information by encoding the demonstrator’s distress response during observational learning, hence enabling acquisition of negative valence of cue by BLA neurons and behavioral output. In order to test their hypothesis, Allsop et al. used an observational fear conditional paradigm to create association between a conditioned stimulus and punishment.

I’m actually curious as to why Allsop et al. did not use the VSDS proposed by Sial et al., since it was published a few years prior. This could merely have been due to a time-related matter—being that behavioral experiments could have commenced before the Sial et al. publication—but it seems as though Sial et al. have solid evidence in favor of the validity of their model. Hence, perhaps a future study would be verifying the impact a more robust (and objectively more traumatizing) observational learning paradigm such as VSDS could have on the ACC-BLA circuit and to what extent corticoamygdala inhibition would impair a more distressing experience.

Sial et al. also discussed one of the caveats of studying VSDS in adolescent mice to be that aggressors are less likely to attack small adolescent mice. Furthermore, the challenge to studying the effects of witnessing social defeat in female mice since males are unlikely to be aggressive when a female is present. Both populations are heavily understudied, and devising successful models geared towards them would have tremendous implications for understanding circumstances such as childhood PTSD in adolescents and domestic violence (etc.) in females. I’d be interested to know if a study involving chronic testosterone treatment of a female and then a reproduction of VSDS with a WT females as intruder and witness would show similar results to what was shown with the adult males. Although I don’t have a proposition for studying adolescents, I do believe a longitudinal study post a VSDS paradigm during development could be a useful tool for understanding the complex neural circuit behind childhood trauma.