Comparisons between operant response and 1,1,1-trichloroethane toxicokinetics in mouse blood and brain.
The effect of 1,1,1-trichloroethane (TRI) inhalation on operant response was evaluated in relation to the concentration of TRI in blood and brain tissue in mice during exposure. Male CD-1 mice were trained to lever-press for an evaporated milk reinforcer on a variable interval (VI 60) schedule for 2 h. Trained mice were then exposed to either 3500 or 5000 ppm TRI for 100 min, and the changes in the schedule-controlled performance were measured. Additional groups of mice were exposed under the same conditions as those used in the behavioral study and sacrificed at various times during exposure, and the blood and brain samples were collected and subsequently analyzed for TRI content by headspace gas chromatography. Uptake of TRI into blood and brain was rapid, with near steady-state levels reached after approximately 40-60 min of exposure. Inhalation of 5000 ppm, but not 3500 ppm TRI was seen to cause inhibition of operant response, starting approximately 30 min following the initiation of inhalation exposure and beginning to recover after 80 min of exposure. The threshold concentrations for the maximal behavioral inhibition were approximately 110 micrograms/g and 130 micrograms/ml in mouse brain and blood, respectively. It appears that in addition to TRI concentrations in blood and brain tissue, the time it takes to reach the apparent threshold TRI concentration was also a determinant for the onset of TRI neurobehavioral depression.
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Department of Pharmacology and Toxicology, College of Pharmacy, University of Georgia, Athens 30602-2356.
Muralidhara
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Dallas
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D000280:Administration, Inhalation; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects*; D008297:Male; D051379:Mice; D014240:Trichloroethanes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*
D014240:Trichloroethanes; C024566:1,1,1-trichloroethane