Nicotine effects on the impact of stress

Abstract : This report describes progress in Year 3 of our 3-year award, which is designed to use animal models to understand how nicotine (ingested by Warfighters via smoking or chewing tobacco) affects vulnerability to develop post-traumatic stress disorder (PTSD). As reported previously, we have completed studies in which rats voluntarily self-administer nicotine to the point of dependence, receive fear conditioning (training), and are tested for fear responses 10 days later with no additional access to nicotine. This experimental design is intended to model Warfighters who use nicotine during service but later quit. We find that rats which voluntarily self-administer nicotine and are exposed to a stressor (footshock) soon after intake have abnormally reduced responses to environments previously associated with the stressor, which we term context-potentiated startle (CPS) , but no differences in the ability to learn the association between a discrete cue (a light) and the stressor, which we term fear-potentiated startle (FPS) . Projected to Warfighters, this suggests that self-administered nicotine is producing some anti-anxiety (beneficial) effects under these specific conditions. We also find that rats which voluntarily selfadminister nicotine and are exposed to a stressor after a missed dose (i.e., during withdrawal) have abnormally persistent CPS, but no differences in FPS. Projected to Warfighters, this suggests that nicotine withdrawal is unambiguously detrimental. We now report that we have examined other permutations of our experimental design, including those in which access to nicotine is sustained for long periods of time between training and testing. Our findings with this design were conceptually similar to those when nicotine self-administration ceased: nicotine may have some beneficial effects, but nicotine withdrawal is unambiguously detrimental. Our funding period ended on August 31, 2015 before all of our experiments had been completed.