Nicotine Effects on the Impact of Stress

This final report describes progress and accomplishments in Years 1-3 of our 3-year award, which was 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. We 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 self-administer nicotine and are exposed to a stressor during nicotine withdrawal i.e., caused by a missed dose of nicotine have abnormally persistent CPS, but no differences in FPS. Projected to warfighters, this suggests that nicotine withdrawal is unambiguously detrimental. We also 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.