A rat model of neurobehavioral sensitization to toluene.

Some individuals report that, following either a single high-level or repeated lower-level exposures to chemicals (initiation), subsequent exposure to very low concentrations of chemicals (triggering) produces a variety of adverse effects, including disruption of cognitive processes. Our objective was to model this two-step process in a laboratory animal. Two groups of 16 rats, eight male and eight female, received whole-body inhalation exposure to toluene, either at 80 ppm for 6 h/day for 4 weeks (Repeat group) or to 1600 ppm for 6 h/day on one day only (Acute group). Two other groups (Trigger group and Clean group) of 16 were sham-exposed. After 17 days without toluene exposure, the Acute, Repeat and Trigger groups began a series of daily toluene 'trigger' exposures (10 ppm for 1 h) followed immediately by testing on an operant repeated-acquisitions task requiring learning within and across sessions. The Clean group was sham-exposed prior to operant testing. Trigger or sham exposures and operant testing continued 5 days/week for 17 sessions. Analysis of variance revealed a variety of statistically significant (P < 0.05) differences between treatment groups. Furthermore, the patterns of differences between groups differed (P < 0.05) for female and male rats. For example, male rats of the Trigger group made the most responses, and female rats of the Repeat group responded most slowly. The observation of important changes in the operant behavior of female and male rats previously exposed to toluene, at relatively low concentrations (80 or 1600 ppm) and then later re-exposed at very low concentrations (10 ppm), is consistent with the experiences of humans reporting cognitive difficulties following acute or chronic exposures to chemicals.