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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA008391-09
Application #
6489472
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Lynch, Minda
Project Start
1993-07-01
Project End
2004-12-31
Budget Start
2002-01-01
Budget End
2003-06-30
Support Year
9
Fiscal Year
2002
Total Cost
$278,533
Indirect Cost
Name
University of Chicago
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Zacny, James P; Jun, Jenny M (2010) Lack of sex differences to the subjective effects of nitrous oxide in healthy volunteers. Drug Alcohol Depend 112:251-4
Zacny, James P; Walker, Diana J; Drum, Melinda et al. (2008) Choice of sevoflurane and its subjective and psychomotor effects in light and moderate drinkers. Drug Alcohol Depend 94:101-8
Zacny, James P; Walker, Diana J; Derus, Lindsay M (2008) Choice of nitrous oxide and its subjective effects in light and moderate drinkers. Drug Alcohol Depend 98:163-8
Beckman, Nancy J; Zacny, James P; Walker, Diana J (2006) Within-subject comparison of the subjective and psychomotor effects of a gaseous anesthetic and two volatile anesthetics in healthy volunteers. Drug Alcohol Depend 81:89-95
Walker, Diana J; Beckman, Nancy J; Zacny, James P (2004) Reinforcing and subjective effects of the volatile anesthetic, sevoflurane. Drug Alcohol Depend 76:191-201
Walker, Diana J; Zacny, James P (2003) Bitonic dose-response functions for reinforcing and self-reported effects of nitrous oxide in humans. Pharmacol Biochem Behav 74:851-7
Walker, Diana J; Zacny, James P (2002) Analysis of the reinforcing and subjective effects of different doses of nitrous oxide using a free-choice procedure. Drug Alcohol Depend 66:93-103
Zacny, James P; Hurst, Rebecca J; Graham, Lou et al. (2002) Preoperative dental anxiety and mood changes during nitrous oxide inhalation. J Am Dent Assoc 133:82-8
Walker, D J; Zacny, J P (2001) Within- and between-subject variability in the reinforcing and subjective effects of nitrous oxide in healthy volunteers. Drug Alcohol Depend 64:85-96
Walker, D J; Zacny, J P (2001) Lack of effects of ethanol pretreatment on the abuse liability of nitrous oxide in light and moderate drinkers. Addiction 96:1839-45

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