Shelton Keith L
Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, P.O. Box 980613, Richmond, VA 23298-0613, USA.
Psychopharmacology (Berl). 2009 Apr;203(2):431-40. doi: 10.1007/s00213-008-1380-8. Epub 2008 Oct 30.
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.
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.
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.
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.
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.
由于许多吸入剂的毒性使得无法在人体中进行评估，药物辨别作为主观效应的动物模型，可用于深入了解其尚未被充分理解的与滥用相关的效应。
本研究的目的是训练一种已知具有滥用可能性的原型吸入剂1,1,1 - 三氯乙烷（TCE），使其在小鼠中作为辨别刺激物，并将其与其他类别的吸入剂进行比较。
八只B6SJLF1/J小鼠被训练辨别吸入12000 ppm TCE蒸汽10分钟与空气，七只小鼠被训练辨别4000 ppm TCE与空气。然后进行测试以表征TCE的辨别刺激，并将其与代表性的芳香烃和氯代烃蒸汽、挥发性卤代麻醉剂以及一种气味化合物进行比较。
只有12000 ppm TCE与空气辨别组在替代测试中表现出足够的辨别准确性。TCE蒸汽浓度和暴露时间依赖性地替代了12000 ppm TCE蒸汽训练刺激。三氯乙烯、甲苯、恩氟烷和七氟烷产生了完全替代。其他挥发性测试化合物产生了不同程度的部分替代。气味剂2 - 丁醇没有对TCE产生任何替代。
TCE的辨别刺激效应被氯代烃和芳香烃以及卤代挥发性麻醉剂全部或部分共享。然而，这些化合物在数量和质量上都可以与TCE区分开来。似乎相似程度不仅仅是化学分类的函数，还可能取决于各个化合物的神经化学效应。
