Schedule-controlled operant behavior of rats during 1,1,1-trichloroethane inhalation: relationship to blood and brain solvent concentrations.
The central nervous system is the principal target of 1,1,1-trichloroethane (TRI), and several studies of this volatile solvent have demonstrated effects on learned animal behaviors. There have been few attempts, however, to quantitatively relate such effects to blood or target organ (brain) solvent concentrations. Therefore, Sprague-Dawley rats trained to lever-press for evaporated milk on a variable interval 30-s reinforcement schedule were placed in an operant test cage and exposed to clean air for 20 min, followed by a single concentration of TRI vapor (500-5000 ppm) for 100 min. Additional rats were exposed to equivalent TRI concentrations for 10, 20, 40, 60, 80, or 100 min to determine blood and brain concentration vs. time profiles. Inhalation of 1000 ppm slightly increased operant response rates, whereas 2000, 3500, and 5000 ppm decreased operant response rates in a concentration- and time-dependent manner. Accumulation of TRI in blood and brain was rapid and concentration dependent, with the brain concentration roughly twice that of blood. Plots of blood and brain TRI concentrations against operant performance showed responding in excess of control rates at low concentrations, and decreasing response rates as concentrations increased. Linear regression analyses indicated that blood and brain concentrations, as well as measures of time integrals of internal dose, were strongly correlated with operant performance. Neurobehavioral toxicity in laboratory animals, as measured by changes in operant performance, can therefore be quantitatively related to internal measures of TRI exposure to enhance its predictive value for human risk assessment.
Warren
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Department of Pharmacology and Toxicology, College of Pharmacy, University of Georgia, Athens 30602-2356, USA. terra@polaris.net
Reigle
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Muralidhara
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S
Dallas
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CE
D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects*; D019570:Inhalation Exposure; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000493:pharmacokinetics / Q000633:toxicity*; D014240:Trichloroethanes / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*
D012997:Solvents; D014240:Trichloroethanes; C024566:1,1,1-trichloroethane