Evaluation of 1,1,1-trichloroethane and flurothyl locomotor effects following diazepam treatment in mice.

The abused volatile solvent 1,1,1-trichloroethane (TCE) shares many acute behavioral effects with central nervous system (CNS) depressants; however, demonstration of tolerance to these effects has been difficult. The purpose of the present study was to investigate the development of TCE-induced changes in locomotor activity in mice following repeated injections with diazepam. In the initial concentration-effect curve determinations, diazepam decreased locomotor activity at all doses tested and TCE produced a biphasic effect, increasing locomotor activity at lower concentrations with return to control levels at a high (16,000 ppm) concentration. Flurothyl, a vapor with convulsive properties, had no pronounced effects on locomotor activity at subconvulsant concentrations. Following four daily injections with vehicle or with 10 mg/kg/day diazepam, mice were administered the same concentration of drug/inhalant that they received initially and were retested for locomotor activity effects. Concentration-effect curves for diazepam and flurothyl were not altered by this modest regimen of repeated dosing with diazepam. In contrast, sensitization to the locomotor-stimulating effects of TCE was observed in diazepam-treated mice, but not in vehicle-treated mice. These results suggest that the development of sensitization to TCE involves common mechanisms with those that are affected by repeated dosing with the CNS depressant diazepam.