Pharmacological characterization of the discriminative stimulus of inhaled 1,1,1-trichloroethane.
نویسنده
چکیده
The present study examined the involvement of the GABAA, N-methyl-D-aspartate (NMDA), nicotinic acetylcholine, and mu-opioid receptor systems in the transduction of the discriminative stimulus effects of the abused inhalant 1,1,1-trichloroethane (TCE). Sixteen B6SJLF1/J mice were trained to discriminate 10 min of exposure to 12,000-ppm inhaled TCE vapor from air. Substitution and antagonism tests and TCE blood concentration analysis were subsequently conducted. TCE blood concentrations decreased rapidly after cessation of exposure, falling by 66% within 5 min. TCE vapor concentration-dependently substituted for the 12,000-ppm training stimulus. The volatile anesthetic halothane concentration-dependently and fully substituted for TCE. The benzodiazepine midazolam partially substituted for TCE, producing a maximum of 68% TCE-lever selection. The benzodiazepine antagonist flumazenil attenuated midazolam substitution for TCE, but not the discriminative stimulus effects of TCE itself. The noncompetitive NDMA receptor antagonists phencyclidine and dizocilpine failed to substitute for TCE. Nicotine and the central nicotinic receptor antagonist mecamylamine also failed to produce any TCE-lever selection, nor did they antagonize the discriminative stimulus of TCE. The mu-opioid receptor agonist morphine did not substitute for TCE. The opioid antagonist naltrexone failed to antagonize the discriminative stimulus of TCE. Overall, the present results, combined with previous studies, suggest that the discriminative stimulus effects of TCE are mediated primarily by positive GABAA receptor modulatory effects though a mechanism distinct from the benzodiazepine binding site.
منابع مشابه
2. Relevance to Public Health 2.1 Background and Environmental Exposures to 1,1,1-trichloroethane in the United States
1,1,1-Trichloroethane is a synthetic chemical. In 2003, the estimated capacity of the commercial production of 1,1,1-trichloroethane in the United States was 510 million pounds. Under the Clean Air Act as amended in 1990, all production of 1,1,1-trichloroethane for domestic use was scheduled to cease as of January 1, 2002. It may be used for essential applications such as medical devices and av...
متن کاملDegradation pathways of trichloroethylene and 1,1,1-trichloroethane by Mycobacterium sp. TA27.
We analyzed the kinetics and metabolic pathways of trichloroethylene and 1,1,1-trichloroethane degradation by the ethane-utilizing Mycobacterium sp. TA27. The apparent Vmax and Km of trichloroethylene were 9.8 nmol min(-1) mg of cells(-1) and 61.9 microM, respectively. The apparent Vmax and Km of 1,1,1-trichloroethane were 0.11 nmol min(-1) mg of cells(-1) and 3.1 microM, respectively. 2,2,2-tr...
متن کاملEffects of trichloroethylene, 1,1,1-trichloroethane and carbon tetrachloride on plasma lipoproteins of rats.
Effects of single intraperitoneal administration of trichloroethylene, 1,1,1-trichloroethane, and carbon tetrachloride (positive control) on the plasma contents of lipoproteins were investigated in rats. Plasma was fractionated to VLDL, LDL, and HDL by sequential ultracentrifugation. On the administration of carbon tetrachloride at 30 to 1000 mg/kg, VLDL and HDL were reduced dose-dependently, b...
متن کاملValue of the simultaneous determination of PCO2 in monitoring exposure to 1,1,1-trichloroethane by breath analysis.
Eight volunteers were exposed for eight hours to about 200 ppm of 1,1,1-trichloroethane. On the next morning five series of five alveolar samples were collected for the simultaneous determination of PCO2 and 1,1,1-trichloroethane concentration. Three different methods of sampling were used: voluntary hyperventilation, 10-s breathholding, and "standard." A linear relationship between the alveola...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of pharmacology and experimental therapeutics
دوره 333 2 شماره
صفحات -
تاریخ انتشار 2010