The voluntary inhalation of organic solvents and other vaolatile chemicals remains a significant public health problem. Very little is known concerning the type of intoxication produced by these chemicals and whether or not the effects of all abused inhalants are similar. The hypothesis to be evaluated in this proposed research is that some of the inhaled solvents produce acute intoxications similar to those produced by central nervous system depressants such as alcohol and the barbiturates and/or volatile anesthetics such as halothane. Studies of the discriminative stimulus properties of abused solvents in mice will be used as the model for acute intoxication effects. The following questions will be addressed. Do the abused inhalants toluene, 1,1,1-trichloroethane, and isobutyl nitrite produce discriminative stimulus effects similar to pentobarbital, ethanol, and/or halothane which may explain their self-administration? Do all abused solvents and inhaled compounds have similar acute discriminative stimulus effects? What are the relative potencies of abused inhalants? Does administration of solvents by injection and by inhalation result in different effects? What are the important exposure parameters determining solvent effects by inhalation? What methodologies are most appropriate for studying the acute behavioral effects of inhaled compounds in the laboratory. Answers to these questions will significantly help our understanding of the solvent abuse phenomenon, and may lead to altered prevention and treatment strategies. Also, comparisons of various solvents will help identify those with significant abuse potential. Finally, the discovery of commonalities in the effects of abused solvents, alcohol, anesthetics, and classical CNS depressants such as the barbiturates will have implications for theories on the neurobiology of the abuse of depressant drugs and specifically on theories for the cellular mechanisms of action for these compounds. Because abused solvents share properties with both alcohol and abused depressant drugs, studies of solvents may provide a basis for bringing together the research on substance abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA003112-01A1
Application #
3207707
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1985-01-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
Overall Medical
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Bowen, Scott E; Balster, Robert L (2006) Tolerance and sensitization to inhaled 1,1,1-trichloroethane in mice: results from open-field behavior and a functional observational battery. Psychopharmacology (Berl) 185:405-15
Donny, Eric C; Lanza, Stephanie T; Balster, Robert L et al. (2004) Using growth models to relate acquisition of nicotine self-administration to break point and nicotinic receptor binding. Drug Alcohol Depend 75:23-35
Gerasimov, M R (2004) Brain uptake and biodistribution of [11C]toluene in nonhuman primates and mice. Methods Enzymol 385:334-49
Blokhina, Elena A; Dravolina, Olga A; Bespalov, Anton Y et al. (2004) Intravenous self-administration of abused solvents and anesthetics in mice. Eur J Pharmacol 485:211-8
Lanza, Stephanie T; Donny, Eric C; Collins, Linda M et al. (2004) Analyzing the acquisition of drug self-administration using growth curve models. Drug Alcohol Depend 75:11-21
Cruz, Silvia Lorenia; Gauthereau, Marcia Yvette; Camacho-Munoz, Cynthia et al. (2003) Effects of inhaled toluene and 1,1,1-trichloroethane on seizures and death produced by N-methyl-D-aspartic acid in mice. Behav Brain Res 140:195-202
Bespalov, Anton; Sukhotina, Irina; Medvedev, Ivan et al. (2003) Facilitation of electrical brain self-stimulation behavior by abused solvents. Pharmacol Biochem Behav 75:199-208
Gerasimov, Madina R; Collier, Lauren; Ferrieri, Abbie et al. (2003) Toluene inhalation produces a conditioned place preference in rats. Eur J Pharmacol 477:45-52
Balster, Robert L; Bigelow, George E (2003) Guidelines and methodological reviews concerning drug abuse liability assessment. Drug Alcohol Depend 70:S13-40
Wiley, Jenny L; Bale, Ambuja S; Balster, Robert L (2003) Evaluation of toluene dependence and cross-sensitization to diazepam. Life Sci 72:3023-33

Showing the most recent 10 out of 48 publications