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.
