Comparisons between operant response and 1,1,1-trichloroethane toxicokinetics in mouse blood and brain. 1994

L You, and S Muralidhara, and C E Dallas
Department of Pharmacology and Toxicology, College of Pharmacy, University of Georgia, Athens 30602-2356.

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.

UI MeSH Term Description Entries
D008297 Male Males
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003216 Conditioning, Operant Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced. Instrumental Learning,Learning, Instrumental,Operant Conditioning,Conditionings, Operant,Instrumental Learnings,Learnings, Instrumental,Operant Conditionings
D000280 Administration, Inhalation The administration of drugs by the respiratory route. It includes insufflation into the respiratory tract. Drug Administration, Inhalation,Drug Administration, Respiratory,Drug Aerosol Therapy,Inhalation Drug Administration,Inhalation of Drugs,Respiratory Drug Administration,Aerosol Drug Therapy,Aerosol Therapy, Drug,Drug Therapy, Aerosol,Inhalation Administration,Administration, Inhalation Drug,Administration, Respiratory Drug,Therapy, Aerosol Drug,Therapy, Drug Aerosol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014240 Trichloroethanes Chlorinated ethanes which are used extensively as industrial solvents. They have been utilized in numerous home-use products including spot remover preparations and inhalant decongestant sprays. These compounds cause central nervous system and cardiovascular depression and are hepatotoxic. Include 1,1,1- and 1,1,2-isomers.
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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