Tolerance and sensitization to inhaled 1,1,1-trichloroethane in mice: results from open-field behavior and a functional observational battery

Rationale: 1,1,1-Trichloroethane (TCE), a representative abused solvent, has well described acute behavioral effects in animals. Much less is known about repeated high-concentration exposures as would be encountered in inhalant abusers. Tolerance has been demonstrated in some, but not all, studies with TCE while sensitization has also been seen with other abused solvents. Objective: The present study was designed to further characterize changes in the effects of repeated exposure to TCE on a variety of mouse behaviors. Results: Mice were tested using locomotor activity as well as a functional observational battery (FOB) both before and after a regimen of daily exposures to various concentrations of TCE. Results: The initial locomotor effects of acute 30-min exposures to TCE were biphasic with concentration-dependent increases in activity at lower concentrations and decreases observed at higher concentrations. The profile of acute effects as measured by the FOB included changes in posture, decreased arousal, disturbances in gait, delayed righting reflexes, and decreased sensorimotor reactivity. Animals were then divided into five groups and exposed 30 min/day to either air or one of four concentrations of TCE (2,000, 6,000, 10,000, or 13,300 ppm) for 15 consecutive days. The TCE concentration used primarily affected the magnitude of change, not whether tolerance or sensitization occurred. Tolerance developed on the measures of forelimb grip strength, inverted screen, and number of rears. Conversely, sensitization developed to measures of locomotor activity. Conclusion: Depending on the behavioral measure, both tolerance and sensitization can occur in mice with repeated exposure to TCE. Both of these phenomena are characteristic of drugs of abuse.