Inhalant abuse remains a problem throughout the world. There is a limited amount of research in the area of behavioral pharmacology of inhalants, and that scant research is predominantly nonhuman in nature. We have attempted over the last seven years to characterize the behavioral effects (subjective, psychomotor and reinforcing) of an inhalant that is abused by humans, nitrous oxide, and to understand those variables which may modulate the behavioral effects of this gaseous anesthetic in healthy volunteers. We wish to continue to characterize nitrous oxide in the present grant application, but to also extend our research to the class of volatile inhaled general anesthetics. We are extending our research to encompass volatile inhaled anesthetics because volatile anesthetics are 1) abused and 2) similar to a number of other volatile inhalants that are also abused (e.g., toluene and trichloroethane, which are contained in various commercial products including adhesives, aerosol sprays, and cleaning/degreasing agents) but cannot be safely or ethically studied in humans. Specifically, in this grant, we propose two series of studies. The first series of studies will examine the reinforcing and subjective effects of sevoflurane, a prototypic volatile anesthetic, and nitrous oxide and potential variables that may modulate those effects, including time of day, informational set, and drug use history. In the second series we propose to characterize the subjective and psychomotor impairing effects of nitrous oxide and sevoflurane, and to compare and contrast their effects to each other as well as to other drugs of abuse. By including other drugs of abuse, we will be able to compare and contrast states of intoxication from different drugs to determine which drugs nitrous oxide and sevoflurane most resemble. Because volatile anesthetics have been shown to be similar to other frequently abused inhalants (e.g., toluene, 1,l,1 trichloroethane) [Evans and Balster, 1991; Balster, 1997, 1998], our results with the volatile anesthetic, sevoflurane, should give an indication of the state of intoxication of other inhalants. In addition, such information will shed light on the possible neurochemical mechanisms of action mediating the intoxicating effects of nitrous oxide, sevoflurane, and related inhalants (e.g., toluene, 1,1,1 trichloroethane). In short, in our two proposed series of studies, we are developing a human laboratory model of inhalant abuse by studying potential determinants of abuse liability of inhalants (volatile and gaseous) in healthy volunteers.
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