Characterizing tolerance to trichloroethylene (TCE): effects of repeated inhalation of TCE on performance of a signal detection task in rats.

Previous work showed that rats develop tolerance to the acute behavioral effects of trichloroethylene (TCE) on signal detection if they inhale TCE while performing the task and that this tolerance depends more upon learning than upon changes in metabolism of TCE. The present study sought to characterize this tolerance by assessing signal detection in rats during three phases of TCE exposures. Tolerance was induced in Phase 1 (daily 1-h test sessions concurrent with TCE exposure), extinguished in Phase 2 (daily tests in air with intermittent probe tests in TCE), and reinduced in Phase 3. Original induction in Phase 1 required 2 weeks, whereas reinduction in Phase 3 required less than 1 week. Tolerance persisted for 2 (accuracy) or 8 weeks [response time] in Phase 2 and was resistant to changes in test conditions in Phase 3. The slow induction, gradual extinction, savings during reinduction and lack of disruption from altered test conditions suggest mediation by instrumental learning processes. These data and most other evidence for behavioral tolerance to solvents can be explained by solvent-induced loss of reinforcement.