The abuse by inhalation of organic solvents and other volatile chemicals is a significant public health problem. Very little is known about the types of intoxication produced by these chemicals nor whether the effects of all abused inhalants are similar. In previous years of this grant it was found that a number of abused inhalants produced behavioral effects in animals that were similar to those of the abused depressant drugs pentobarbital and alcohol. Others produced qualitatively different behavioral effects. We propose to continue our studies of the behavioral effects of abused inhalants. Drug discrimination studies in mice will be used as a model for acute intoxication effects in humans. It is proposed to continue to compare the discriminative stimulus effects of additional classes of inhalant chemicals to those of pentobarbital, ethanol and oxazepam. We will carry out in-depth studies of those classes which appear to produce qualitatively different effects from the depressant-like inhalants such as toluene and trichloroethane. This will include further research with the abused volatile nitrites. We propose to study the anti- anxiety effects of inhalants by determining their ability to block a discrimination based upon an anxiogenic agent, pentylenetetrazol. We also proposed to undertake studies of the cellular mechanisms for the discriminative stimulus effects of inhalants by studying selective antagonists. In addition, we propose to train subjects to discriminate certain inhalants from air to use as an additional model for inhalant effects. We will also begin to characterize the critical exposure parameters for selected inhalants that determine their behavioral effects. Lastly, we propose to investigate the possible biological vulnerability to inhalant effects and to further test our hypothesis that inhalants produce alcohol- like effects by testing for sensitivity differences in strains of mice which differ in alcohol sensitivity. Overall, these studies will provide information on the abuse potential of inhalants and on the mechanisms for their behavioral effects.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003112-08
Application #
3207714
Study Section
Special Emphasis Panel (SRCD (08))
Project Start
1985-01-01
Project End
1993-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Type
Schools of Medicine
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
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
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

Showing the most recent 10 out of 48 publications