CO₂ reactivity is associated with individual differences in appetitive extinction memory

Pavlovian conditioning can underly the maladaptive behaviors seen in psychiatric disorders such as anxiety and addiction. In both the lab and the clinic, these responses can be attenuated through extinction learning, but often return with the passage of time, stress, or a change in context. Extinction to fear and reward cues are both subject to these return of behavior phenomena and have overlap in neurocircuitry, yet it is unknown whether they share any common predictors. The orexin system has been implicated in both fear and appetitive extinction and can be activated through a CO₂ challenge. We previously found that behavioral CO₂ reactivity predicts fear extinction and orexin activation. Here, we sought to extend our previous findings to determine whether CO₂ reactivity might also predict extinction memory for appetitive light-food conditioning. We find that the same subcomponent of behavioral CO₂ reactivity that predicted fear extinction also predicts appetitive extinction, but in the opposite direction. We show evidence that this subcomponent remains stable across two CO₂ challenges, suggesting it may be a stable trait of both behavioral CO₂ reactivity and appetitive extinction phenotype. Our findings further the possibility for CO₂ reactivity to be used as a transdiagnostic screening tool to determine whether an individual would be a good candidate for exposure therapy.