Inhaled 1,1,1-trichloroethane-produced physical dependence in mice: effects of drugs and vapors on withdrawal.
1,1,1-Trichloroethane (TCE), a widely used and abused solvent, was investigated for its ability to produce physical dependence in mice. Cessation of 4 days of continuous inhalation of TCE (500-4000 ppm) resulted in a withdrawal syndrome characterized by handling-induced convulsions and increased susceptibility to pentylenetetrazol-induced convulsions. The severity of withdrawal convulsions was diminished by 30 to 60 min of reexposure to 2000 to 4000 ppm TCE or to the vapor of another widely used and abused solvent, toluene (1000-2000 ppm). Ethanol (1-2 g/kg), midazolam (0.3-1 mg/kg) and pentobarbital (30 mg/kg) were also effective in decreasing the withdrawal severity; however, chlorpromazine (3 mg/kg) and phenytoin (30 mg/kg) were without effects. These data suggest that TCE has the ability to produce physical dependence of the central nervous system depressant drug type. Taken together with other evidence for similarities in the pharmacological and behavioral effects of TCE and depressant drugs of abuse, these data support the hypothesis that the basis for TCE abuse may be its ability to produce ethanol- and depressant drug-like effects.
Evans
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EB
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Balster
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RL
D000280:Administration, Inhalation; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008874:Midazolam / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D019966:Substance-Related Disorders; D014050:Toluene / Q000494:pharmacology; D014240:Trichloroethanes / Q000009:adverse effects*; D014835:Volatilization
D014240:Trichloroethanes; C024566:1,1,1-trichloroethane; D014050:Toluene; D000431:Ethanol; D010672:Phenytoin; D010424:Pentobarbital; D008874:Midazolam; D002746:Chlorpromazine