Inhalation of volatile substances for their pharmacologic effects is relatively common among young people and is often associated with concurrent use of other drugs, especially alcohol and marihuana. Although there is concern that early solvent use, alone or in conjunction with other drugs, may promote subsequent substance abuse, there is only fragmentary epidemiologic evidence to justify this concern. However, recent experiments with rats suggest an interactive effect between the most frequently abused solvent--toluene--and alcohol that results in a marked increase in preference for alcohol. The purpose of the proposed research is to confirm this interactive effect between toluene and alcohol and to systematically examine the exposure conditions for both substances that are necessary and/or sufficient to elicit this effect. The possible involvement of tolerance to and dependence on either substance, or both, will also be examined. Finally, other commonly inhaled solvents will be examined to determine their liability in this regard. The general experimental protocol will be to expose groups of male, weanling Fischer rats to fresh air, with or without concurrent access to alcohol, or to solvent, with or without access to alcohol. Subsequent preference for alcohol will be tested by a 2-bottle choice method. The main experimental conditions to be manipulated will be (1) solvent exposure concentration; (2) daily exposure schedule; (3) number of exposures; (4) alcohol concentration during solvent exposure and in preference tests thereafter; and (5) availability of water during solvent exposure (i.e., forced versus free-choice alcohol). In some experiments, tests for tolerance and cross-tolerance will be conducted. In others, the possible development of physical dependence on alcohol and/or the solvent, defined by an abstinence syndrome, will be examined. The results of these experiments will provide important and comprehensive evidence to support, or deny, the concern that early solvent use, alone or in conjunction with alcohol, increases the risk of subsequent alcohol abuse. They will also provide a data base for designing experiments to determine the possible metabolic, pharmacologic, and neurochemical mechanisms involved.
