EXCEED THE SPACE PROVIDED. Chemical intolerance (CI) in humans is defined as the inability to tolerate environmental chemicals due to experience of symptoms associated with those chemicals, and these individualsreport that prior chemical exposures produced an increased sensitivity to subsequent exposures. To date, there are no clear clinicaldata that validate whether repeated chemical exposure causes the development of CI in a sensitive subpopulation. Recent work shows that a substantial subset of individuals with CI report a constellation of symptoms that mimic those found in panic disorder and posttraumatic stress disorder (PTSD). Our studies in animalssupport several investigators' hypotheses that CI may develop as an anxiety disorder akin to panic disorder or an atypical form of PTSD. However, few animal models for CI have been explored. The proposed work emphasizes the parallels between panic disorder/PTSD and CI in the development of a potential animal model for CI. We have recently found that repeated, low-level chemical exposure (formaldehyde [Form] exposure, 0.7-2.4 ppm) produces increased conditioned fear responding to odor previously paired with footshock, with a decreased ability to extinguish this fear response. In addition, repeated Form exposure produced increases in corticosterone levels, and behavioral avoidance patterns that suggest that Form may be acting as a stressor. The proposed work will focus on three behaviors, conditioned freezing behavior, unconditionedanxiety
