Solvent abuse is a growing worldwide problem associated with serious health and social cost. Although inhalant abuse has been shown to meet the DSM-IV diagnostic criteria for drug dependence, its etiology has not been thoroughly investigated. Considering the prevalence of inhalant abuse and the mounting evidence that volatile substance abuse increases the likelihood of adolescents to develop other substance abuse disorders, good animal models for studying inhalant reward mechanisms are strongly needed. To investigate the mechanisms underlying the abuse liability of inhalants, we have recently developed a vapor-exposure conditioned place preference apparatus that is suitable for investigating inhalants in rodents. For our conditioned place preference studies we have chosen to use toluene, the main psychotropic component found in most abused solvent mixtures. Our preliminary studies indicate that toluene produces a significant conditioned place preference in rats, similar to other drugs-of-abuse. In this Exploratory/Developmental Grant proposal we will extend this observation with the following objectives: (1) optimize the paradigm for observing a conditioned place preference to toluene, (2) test the hypothesis that rats will develop a behavioral sensitization to toluene, similar to that for other drugs-of-abuse, and (3) test the hypothesis that animals that have already developed a conditioned place preference to toluene will also self administer this compound by inhalation. The proposed work will build on our established interest in inhalant abuse research and provide a much-needed animal model for inhalant abuse. Subsequent studies would use this animal model to determine the relative abuse potential of different solvents and to correlate this with the potency of these inhalants at likely neurobiological targets, such as ion channels and receptors. Additionally, an animal model for inhalant abuse will aid further exploration of the factors contributing to the predisposition, development and potential treatment of inhalant abuse.
| Lee, Dianne E; Gerasimov, Madina R; Schiffer, Wynne K et al. (2006) Concentration-dependent conditioned place preference to inhaled toluene vapors in rats. Drug Alcohol Depend 85:87-90 |
