Carbon Dioxide Reactivity Differentially Predicts Fear Expression After Extinction and Retrieval-Extinction in Rats.

BACKGROUND

Cues present during a traumatic event may result in persistent fear responses. These responses can be attenuated through extinction learning, a core component of exposure therapy. Exposure/extinction is effective for some people, but not all. We recently demonstrated that carbon dioxide (CO) reactivity predicts fear extinction memory and orexin activation and that orexin activation predicts fear extinction memory, which suggests that a CO challenge may enable identification of whether an individual is a good candidate for an extinction-based approach. Another method to attenuate conditioned responses, retrieval-extinction, renders the original associative memory labile via distinct neural mechanisms. The purpose of the current study was to examine whether we could replicate previous findings that retrieval-extinction is more effective than extinction at preventing the return of fear and that CO reactivity predicts fear memory after extinction. We also examined whether CO reactivity predicts fear memory after retrieval-extinction.

METHODS

Male rats first underwent a CO challenge and fear conditioning and were assigned to receive either standard extinction ( = 28) or retrieval-extinction ( = 28). Then, they underwent a long-term memory (LTM) test and a reinstatement test.

RESULTS

We found that retrieval-extinction resulted in lower freezing during extinction, LTM, and reinstatement than standard extinction. Using the best subset approach to linear regression, we found that CO reactivity predicted LTM after extinction and also predicted LTM after retrieval-extinction, although to a lesser degree.

CONCLUSIONS

CO reactivity could be used as a screening tool to determine whether an individual may be a good candidate for an extinction-based therapeutic approach.