The abuse by inhalation of organic solvents and other volatile chemicals is a significant public health problem. Very little is known about the types of intoxication produced by these chemicals nor whether the effects of all abused inhalants are similar. In previous years of this grant it was found that a number of abused inhalants produced behavioral effects in animals that were similar to those of the abused depressant drugs pentobarbital and alcohol. Others produced qualitatively different behavioral effects. We propose to continue our studies of the behavioral effects of abused inhalants. Drug discrimination studies in mice will be used as a model for acute intoxication effects in humans. It is proposed to continue to compare the discriminative stimulus effects of additional classes of inhalant chemicals to those of pentobarbital, ethanol and oxazepam. We will carry out in-depth studies of those classes which appear to produce qualitatively different effects from the depressant-like inhalants such as toluene and trichloroethane. This will include further research with the abused volatile nitrites. We propose to study the anti- anxiety effects of inhalants by determining their ability to block a discrimination based upon an anxiogenic agent, pentylenetetrazol. We also proposed to undertake studies of the cellular mechanisms for the discriminative stimulus effects of inhalants by studying selective antagonists. In addition, we propose to train subjects to discriminate certain inhalants from air to use as an additional model for inhalant effects. We will also begin to characterize the critical exposure parameters for selected inhalants that determine their behavioral effects. Lastly, we propose to investigate the possible biological vulnerability to inhalant effects and to further test our hypothesis that inhalants produce alcohol- like effects by testing for sensitivity differences in strains of mice which differ in alcohol sensitivity. Overall, these studies will provide information on the abuse potential of inhalants and on the mechanisms for their behavioral effects.
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