Examination of CO₂ reactivity and orexin activity as predictors of extinction memory for fear, food, and alcohol cues in rats

Abstract

Trauma, anxiety, and substance use disorders are highly prevalent but only half of individuals achieve remission with the best available behavioral treatment, exposure therapy. The ability to identify likely responders to exposure therapy and provide an alternative treatment to likely non-responders would allow a greater number of individuals to achieve remission. To address this, I turned to the laboratory rat to model the associative learning processes that underlie these disorders and exposure therapy to examine behavioral and neural predictors of treatment response. Rats underwent Pavlovian conditioning, extinction training, and long-term memory testing of cues associated with fear (Chapters 3 & 4), food (Chapters 2 & 4), and alcohol (Chapter 5) as well as a CO₂ challenge prior to euthanasia to examine orexin activity in the lateral hypothalamus. Behavioral CO₂ reactivity predicted extinction memory for fear, food, and alcohol cues. CO₂ reactivity also predicted fear and alcohol memories after a different treatment, retrieval-extinction, although to a lesser degree. Orexin activity did not predict extinction memory for fear, food, nor alcohol cues. My studies show that CO₂ reactivity, but not CO₂-induced orexin activity, can be used to predict extinction memory for fear and reward cues. My work provides support for CO₂ reactivity to be examined as a predictor of exposure therapy response in individuals with trauma, anxiety, and substance use disorders.Neuroscienc