title: Behavioral components of tolerance to repeated inhalation of trichloroethylene (TCE) in rats.
abstract: The possibility that the acute neurotoxic effects of organic solvents change with repeated exposure will affect risk assessment of these pollutants. We observed previously that rats inhaling trichloroethylene (TCE) showed a progressive attenuation of impairment of signal detection behavior across several weeks of intermittent exposure, suggesting the development of tolerance. Here, we explored the development of tolerance to TCE during two weeks of daily exposures, and the degree to which learned behavioral modifications ("behavioral tolerance") could account for the effect. Adult Long-Evans rats were trained to perform a visual signal detection task (SDT) in which a press on one lever yielded food if a visual stimulus (a "signal") had occurred on that trial, and a press on a second lever produced food if no signal had been presented. In two experiments, with 2000 and 2400 ppm of TCE respectively, trained rats were divided into two groups (n = 8/group) with equivalent accuracy and then exposed to TCE in two-phase studies. In Phase 1, one group of rats received daily SDT tests paired with 70-min TCE exposures, followed by 70-min exposures to clean air after testing. The other group received daily SDT tests in clean air, followed by 70-min exposures to TCE (unpaired exposure and testing). All rats thus received the same number and daily sequence of exposures to TCE that differed only in the pairing with SDT testing. Both concentrations of TCE disrupted performance of the paired groups and this disruption abated over the 9 days of exposure. In Phase 2, the pairing of exposure and test conditions were reversed for the two groups. The groups that were shifted from unpaired to paired exposures (Unpaired-Paired groups) showed qualitatively similar patterns of deficit and recovery as did the rats whose tests were initially paired with TCE (Paired-Unpaired groups), indicating that task-specific learning was involved in the development of tolerance. Quantitative differences in the magnitude and duration of the effects of TCE in the two groups indicated that other factors, not specific to the SDT, also contributed to the development tolerance to TCE. Published by Elsevier Science Inc.
authors.affiliation: Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. bushnell.philip@epa.gov
authors.forename: P J
authors.initials: PJ
authors.lastname: Bushnell
authors.forename: W M
authors.initials: WM
authors.lastname: Oshiro
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D010775:Photic Stimulation; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D014241:Trichloroethylene / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D014241:Trichloroethylene