Although the abuse of inhalants continues to be a significant public health problem throughout the U.S. and the world, there has been very little systematic examination of the reinforcing properties of these compounds. Therefore, the aim of this research proposal is to investigate and develop a method of inhalant self-administration that can be used long-term in mice to simulate the full array of human behaviors associated with solvent abuse including acquisition, maintenance, extinction and reinstatement of both inhalant-seeking and inhalant-taking behavior. This research will focus on the current hypothesis that a majority of the abused inhalants produce a profile of neurobehavioral effects that are analogous to those produced by abused depressant drugs (e.g. barbiturates, alcohol, benzodiazepines) [Evans and Balster, 1991]. A key objective of this research proposal is the design and implementation of a preclinical model of inhalant self-administration with a primary focus on the abused inhalants toluene and 1,1,1-trichloroethane. We are proposing two series of studies for this grant. In the first series, we propose to characterize the subjective and psychomotor effects of toluene and 1,1,1-trichloroethane and to compare them to other abused inhalants. The information collected from the first series of tests will then be used as a guide for our next series of studies. In the second series of studies, we propose to design and build an apparatus (i.e., a dynamic solvent delivery system interfaced with an operant monitoring system), which will reliably deliver a """"""""dose"""""""" of inhalant on an intermittent basis. Once completed, we will use the system to develop and validate this method of solvent inhalation by training mice to press a lever for inhalant delivery and by varying both the """"""""dose"""""""" of inhalant and the response requirements necessary for obtaining it. Finally, the research described in the present application will extend the knowledge base of psychomotor and subjective effects of abused inhalants. In addition, this research will have important implications for understanding basic mechanisms underlying and controlling inhalant abuse, for the development of treatment medications and behavioral techniques for modifying the abuse of inhalants.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA015095-03
Application #
6729211
Study Section
Special Emphasis Panel (ZRG1-BBBP-1 (01))
Program Officer
Lynch, Minda
Project Start
2002-04-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2006-03-31
Support Year
3
Fiscal Year
2004
Total Cost
$149,000
Indirect Cost
Name
Wayne State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Bowen, Scott E; Kimar, Sarah; Irtenkauf, Susan (2010) Comparison of toluene-induced locomotor activity in four mouse strains. Pharmacol Biochem Behav 95:249-57
Bowen, Scott E; McDonald, Phillip (2009) Abuse pattern of toluene exposure alters mouse behavior in a waiting-for-reward operant task. Neurotoxicol Teratol 31:18-25
Bowen, Scott E (2009) Time course of the ethanol-like discriminative stimulus effects of abused inhalants in mice. Pharmacol Biochem Behav 91:345-50
Bowen, Scott E; Batis, Jeffery C; Paez-Martinez, Nayeli et al. (2006) The last decade of solvent research in animal models of abuse: mechanistic and behavioral studies. Neurotoxicol Teratol 28:636-47
Bowen, Scott E (2006) Increases in amphetamine-like discriminative stimulus effects of the abused inhalant toluene in mice. Psychopharmacology (Berl) 186:517-24
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
Bowen, Scott E; Hannigan, John H (2006) Developmental toxicity of prenatal exposure to toluene. AAPS J 8:E419-24