Inhalant abuse, which includes the general anesthetic gas, nitrous oxide (N2O), has continued to increase since 1975, as determined by two epidemiological databases, the National High School Senior Survey and the National Household Survey on Drug Abuse. The problem of inhalant abuse is worldwide and is not necessarily limited to any particular age group or socioeconomic group. Therefore, understanding the variables which influence the behavioral effects of N2O, especially its reinforcing effects, and understanding the neurochemical substrates of the actions of the drug, continue to be imperative. In past studies, we have examined modulating factors of the reinforcing effects of N2O in healthy volunteers, and we will continue to do so in the present application. In the first series of studies, we will examine the impact of alcohol consumption (light vs. moderate), pain threshold (low vs. high), behavioral contingencies (relax vs. work on tasks), and concomitant administration of other drugs (alcohol, amphetamine) on the reinforcing effects of extended (30 min) inhalation of N2O. In addition, we will examine the reinforcing effects of bolus concentrations of N2O - single breath inhalations is a common way that N2O is used in recreational settings. A key component to many of these studies in the first series is that in a matter of several sessions, we will be able to assess the subjective and reinforcing effects of a full range of subanesthetic doses of N2O - this is normally not possible when assessing other CNS drugs with abuse liability due to their longer acting effects. In the second series of studies, we will investigate possible neurochemical mechanisms that mediate the different effects of N2O, including its analgesic, subjective and psychomotor effects. By using the appropriate drug receptor antagonists, we will focus on those systems which have been implicated as crucial in mediating N2O's effects in animal studies - the opioidergic, GABAergic, and dopaminergic systems. Through these studies, we will continue to gain a better understanding of a drug that falls into a class of abused drugs (inhalants), whose behavioral actions and neurochemical mechanisms related to abuse potential need to be more fully delineated and characterized.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA008391-05
Application #
2443462
Study Section
Special Emphasis Panel (SRCD (27))
Program Officer
Lynch, Minda
Project Start
1993-07-01
Project End
1999-05-31
Budget Start
1997-07-01
Budget End
1998-05-31
Support Year
5
Fiscal Year
1997
Total Cost
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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