In rhesus monkeys, the reinforcing effects of intravenously delivered ethanol lead to high ethanol intake, high ethanol blood levels, marked intoxication, and, under continuous access conditions, """"""""binge"""""""" patterns of ethanol consumption, physiological dependence, and withdrawal signs. These are some of the characteristics of severe human alcoholism, a condition that is likely to result, at least in part, from this pharmacologically based reinforcing effect of ethanol. We suggest that response-contingent delivery of i.v. ethanol is a fairly """"""""pure"""""""" measure of these reinforcing effects of ethanol, relatively unmodified by the aspects of taste, fluid volume, and gastrointestinal absorption that appear to prevent consumption by monkeys of equally large amounts of ethanol by the oral route. We propose to use behavioral economic procedures (demand curves) to quantify these reinforcing effects of i.v. ethanol and to compare them with those of other intravenously delivered drugs. In further studies, these procedures will be used to determine how the combination of ethanol and other drugs of abuse changes the reinforcing effects of both drugs. Because demand functions are unaltered by changes in drug potency, but are modified by changes in drug effectiveness, the measurements should indicate whether the various drug combinations result in a greater reinforcing effectiveness than either drug alone, or whether the potencies of the drugs as reinforcers are enhanced when they are combined. Finally, this same analysis will be used to determine how the treatment drugs of naltrexone and acamprosate modify the reinforcing effects of intravenous ethanol, again either by decreasing its reinforcing effectiveness or by decreasing its potency as a reinforcer. These studies will provide information not currently available on how ethanol compares with other drugs in terms of its reinforcing effectiveness, information that could impact policy decisions regarding legalization or decriminalization of other drugs of abuse. Data relevant to the behavioral and pharmacological mechanisms underlying polydrug abuse involving ethanol, and underlying pharmacological treatment of alcoholism will also be obtained.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA013713-01A1
Application #
6613584
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Egli, Mark
Project Start
2003-05-01
Project End
2007-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
1
Fiscal Year
2003
Total Cost
$489,310
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pharmacology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Winger, Gail; Galuska, Chad M; Hursh, Steven R (2007) Modification of ethanol's reinforcing effectiveness in rhesus monkeys by cocaine, flunitrazepam, or gamma-hydroxybutyrate. Psychopharmacology (Berl) 193:587-98
Wade-Galuska, Tammy; Galuska, Chad M; Winger, Gail et al. (2007) Aspartame demand in rhesus monkeys: effects of volume and concentration manipulations. Behav Processes 74:71-8
Hursh, Steven R; Galuska, Chad M; Winger, Gail et al. (2005) The economics of drug abuse: a quantitative assessment of drug demand. Mol Interv 5:20-8
Winger, Gail; Woods, James H; Galuska, Chad M et al. (2005) Behavioral perspectives on the neuroscience of drug addiction. J Exp Anal Behav 84:667-81