Keith L Shelton1. 1. Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, P.O. Box 980613, Richmond, VA 23298-0613, USA. klshelto@vcu.edu
Abstract
RATIONALE: Because the toxicity of many inhalants precludes evaluation in humans, drug discrimination, an animal model of subjective effects, can be used to gain insights on their poorly understood abuse-related effects. OBJECTIVES: The purpose of the present study was to train a prototypic inhalant that has known abuse liability, 1,1,1-trichloroethane (TCE), as a discriminative stimulus in mice, and compare it to other classes of inhalants. MATERIALS AND METHODS: Eight B6SJLF1/J mice were trained to discriminate 10 min of exposure to 12,000 ppm inhaled TCE vapor from air and seven mice were trained to discriminate 4,000 ppm TCE from air. Tests were then conducted to characterize the discriminative stimulus of TCE and to compare it to representative aromatic and chlorinated hydrocarbon vapors, volatile halogenated anesthetics as well as an odorant compound. RESULTS: Only the 12,000 ppm TCE versus the air discrimination group exhibited sufficient discrimination accuracy for substitution testing. TCE vapor concentration- and exposure time-dependently substituted for the 12,000 ppm TCE vapor training stimulus. Full substitution was produced by trichloroethylene, toluene, enflurane, and sevoflurane. Varying degrees of partial substitution were produced by the other volatile test compounds. The odorant, 2-butanol, did not produce any substitution for TCE. CONCLUSIONS: The discriminative stimulus effects of TCE are shared fully or partially by chlorinated and aromatic hydrocarbons as well as by halogenated volatile anesthetics. However, these compounds can be differentiated from TCE both quantitatively and qualitatively. It appears that the degree of similarity is not solely a function of chemical classification but may also be dependent upon the neurochemical effects of the individual compounds.
RATIONALE: Because the toxicity of many inhalants precludes evaluation in humans, drug discrimination, an animal model of subjective effects, can be used to gain insights on their poorly understood abuse-related effects. OBJECTIVES: The purpose of the present study was to train a prototypic inhalant that has known abuse liability, 1,1,1-trichloroethane (TCE), as a discriminative stimulus in mice, and compare it to other classes of inhalants. MATERIALS AND METHODS: Eight B6SJLF1/J mice were trained to discriminate 10 min of exposure to 12,000 ppm inhaled TCE vapor from air and seven mice were trained to discriminate 4,000 ppm TCE from air. Tests were then conducted to characterize the discriminative stimulus of TCE and to compare it to representative aromatic and chlorinated hydrocarbon vapors, volatile halogenated anesthetics as well as an odorant compound. RESULTS: Only the 12,000 ppm TCE versus the air discrimination group exhibited sufficient discrimination accuracy for substitution testing. TCE vapor concentration- and exposure time-dependently substituted for the 12,000 ppm TCE vapor training stimulus. Full substitution was produced by trichloroethylene, toluene, enflurane, and sevoflurane. Varying degrees of partial substitution were produced by the other volatile test compounds. The odorant, 2-butanol, did not produce any substitution for TCE. CONCLUSIONS: The discriminative stimulus effects of TCE are shared fully or partially by chlorinated and aromatic hydrocarbons as well as by halogenated volatile anesthetics. However, these compounds can be differentiated from TCE both quantitatively and qualitatively. It appears that the degree of similarity is not solely a function of chemical classification but may also be dependent upon the neurochemical effects of the individual compounds.
Authors: Gregory F Lopreato; Rachel Phelan; Cecilia M Borghese; Michael J Beckstead; S John Mihic Journal: Drug Alcohol Depend Date: 2003-05-01 Impact factor: 4.492