Johnson, Philip L.Molosh, Andrei I.Federici, Lauren M.Bernabe, CristianHaggerty, DavidFitz, Stephanie D.Nalivaiko, EugeneTruitt, WilliamShekhar, Anantha2019-07-012019-07-012019-01-22Johnson, P. L., Molosh, A. I., Federici, L. M., Bernabe, C., Haggerty, D., Fitz, S. D., … Shekhar, A. (2019). Assessment of fear and anxiety associated behaviors, physiology and neural circuits in rats with reduced serotonin transporter (SERT) levels. Translational psychiatry, 9(1), 33. doi:10.1038/s41398-019-0368-yhttps://hdl.handle.net/1805/19785Genetic variation in serotonin transporter (SERT) that reduces transcriptional efficiency is associated with higher anxiety and fear traits and a greater incidence of post traumatic stress disorder (PTSD). Although previous studies have shown that rats with no expression of SERT (SERT-/-) have increased baseline anxiety behaviors, SERT+/- rats with low SERT expression (and more relevant to the clinical condition with low SERT expression) do not. Yet, no systematic studies of fear acquisition/extinction or their underlying neural mechanisms have been conducted in this preclinical genetic SERT+/- model. Here we sought to determine if SERT+/- or SERT-/-, compared to wildtype, rats would show exacerbated panic responses and/or persistent conditioned fear responses that may be associated with PTSD or phobia vulnerability. Results: Only SERT-/- rats showed increased baseline anxiety-like behaviors with heightened panic respiratory responses. However SERT+/- (also SERT-/-) rats showed enhanced acquisition of fear and delayed extinction of fear that was associated with changes in serotonergic-related genes (e.g., reduced 5-HT1A receptor) and disrupted inhibition within the basolateral amygdala (BLA). Furthermore, the disrupted fear responses in SERT+/- rats were normalized with 5HT1A antagonist infusions into the BLA. Enhanced acquisition and failure to extinguish fear memories displayed by both SERT-/- and SERT+/- rats are cardinal symptoms of disabling anxiety disorders such as phobias and PTSD. The data here support the hypothesis that reduced SERT function is a genetic risk that disrupts select gene expression and network properties in the amygdala that could result in vulnerability to these syndromes.en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesAmygdalaAnxietyBasolateral Nuclear ComplexRNA-Binding ProteinsArticle