The abuse of inhalants is a significant public health problem in the U.S. and around the world. Unfortunately, this form of drug abuse is the least well understood of all substance abuse problems. This project will attempt to provide scientific information on the following general questions: l) What is the nature of the acute intoxication produced by abused inhalants? 2) How is concentration and exposure duration related to the nature and magnitude of acute effects? 3) Is the profile of acute effects similar to that produced by other drugs of abuse? 4) Do all inhalants produce a similar profile of effects? 5) What can be expected from mixtures of solvents? 6) Does dependence occur with repeated use? 7) Can an assessment of the above properties of inhalants contribute to an understanding, and prediction, of their abuse potential? and 8) What is the neural basis of inhalant effects on behavior? To answer these questions, behavioral test procedures will be used in mice. In previous years of this project it has been found that many abused inhalants produce a profile of behavioral effects very similar to that produced by alcohol and abused depressant drugs, possibly accounting for their abuse. Therefore a major portion of the proposal is to examine the effects of inhalants relative to those of ethanol and other drugs of abuse, and/or in behavioral test procedures specific for this drug class. New behavioral test procedures which will be developed during this project period are methods for studying inhalant self-administration, place preference conditioning, effects on motor activity, multiple-schedule performance, and punished responding. Toluene, trichloroethane (TCE), methoxyflurane, flurothyl and isoamyl nitrite will be evaluated in these new procedures. In the prior project period, a model for producing physical dependence on TCE was developed. It is proposed to further study this model with TCE and other inhalants. It is also proposed to continue to use drug discrimination procedures, inhalant effects on schedule-controlled performance, cross dependence with TCE, and a functional observational battery (FOB) to further study a series of alkylbenzenes. A series of aliphatic hydrocarbons and related isoparaffins will be evaluated for the first time using the FOB, motor activity, and effects on schedule- controlled behavior. The isoparaffin solvents are being considered for addition to many commercial and industrial products to replace TCE, so it will be especially important to study them as soon as possible. Information on the behavioral effects and abuse liability of solvents may allow manufacturers to reformulate products to reduce their abuse.
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