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.
Wiley
Jenny L
JL
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA 23298-0613, USA. jwiley@hsc.vcu.edu
Fagaldé
R Ellis
RE
Bühler
Katriona G
KG
LaVecchia
Kari L
KL
Balster
Robert L
RL
D000818:Animals; D003292:Convulsants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004361:Drug Tolerance / Q000502:physiology; D005481:Flurothyl / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D014240:Trichloroethanes / Q000494:pharmacology*
D003292:Convulsants; D009125:Muscle Relaxants, Central; D014240:Trichloroethanes; C024566:1,1,1-trichloroethane; D005481:Flurothyl; D003975:Diazepam