Repeated Aerosol-vapor JP-8 Jet Fuel Exposure Affects Neurobehavior and Neurotransmitter Levels in a Rat Model

Abstract

Four groups of Fischer Brown Norway hybrid rats were exposed for 5, 10, 15, or 20 d to aerosolized-vapor jet propulsion fuel 8 (JP-8) compared to freely moving (5 and 10-d exposures) or sham-confined controls (15 and 20-d exposures). Behavioral testing utilized the U.S. Environmental Protection Agency Functional Observational Battery. Exploratory ethological factor analysis identified three salient factors (central nervous system [CNS] excitability, autonomic 1, and autonomic 2) for use in profiling JP-8 exposure in future studies. The factors were used as dependent variables in general linear modeling. Exposed animals were found to engage in more rearing and hyperaroused behavior compared to controls, replicating prior JP-8 exposure findings. Exposed animals also showed increasing but rapidly decelerating stool output (autonomic 1), and a significant increasing linear trend for urine output (autonomic 2). No significant trends were noted for either of the control groups for the autonomic factors. Rats from each of the groups for each of the time frames were randomly selected for tissue assay from seven brain regions for neurotransmitter levels. Hippocampal DOPAC was significantly elevated after 4-wk JP-8 exposure compared to both control groups, suggesting increased dopamine release and metabolism. Findings indicate that behavioral changes do not appear to manifest until wk 3 and 4 of exposure, suggesting the need for longitudinal studies to determine if these behaviors occur due to cumulative exposure, or due to behavioral sensitization related to repeated exposure to aerosolized-vapor JP-8.

This study was supported by AFOSR grant F49620-97-1-0217. The authors acknowledge Daniel Deever and Christopher Pettis, Laboratory Assistants, Lung Injury Laboratory, University of Arizona, Tucson, for their unwavering work collecting and entering data throughout this experiment; Frank P. Houston, BS, Arizona Research Laboratories, Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, for his oversight during the brain dissection activities; and Frank L. Siegel, PhD, The Waisman Center, University of Wisconsin-Madison, and Steven E. Kornguth, PhD, The University of Texas at Austin, for their assistance with the neurochemical assays. We also recognize Mary Z. Mays, PhD, and Kimberly Sidora-Arcoleo, PhD, MPH, Arizona State University College of Nursing & Healthcare Innovation, Phoenix, and Iris R. Bell, MD, PhD, Departments of Family and Community Medicine and Psychiatry, Program in Integrative Medicine, and College of Public Health, University of Arizona, Tucson, for their critical review and comments.

Notes

U.S. Environmental Protection Agency. 1998. Neurotoxicity Screening Battery, Series 870 Health Effects Test Guidelines #870.6200.