University of Michigan, Ann Arbor, MI

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Stop Animal Exploitation NOW!
S. A. E. N.
"Exposing the truth to wipe out animal experimentation"

Government Grants Promoting Cruelty to Animals

University of Michigan, Ann Arbor, MI

GAIL D. WINGER - Primate Testing - 2006

Grant Number: 5R01AA013713-04
Project Title: Measuring and Modifying Ethanol's Reinforcing Effects
PI Information: RESEARCH PROFESSOR GAIL D. WINGER, gwinger@umich.edu 

Abstract: DESCRIPTION (provided by applicant): 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.

Thesaurus Terms:
ethanol, psychometrics, psychopharmacology, reinforcer, substance abuse related behavior
acamprosate, alcoholic beverage consumption, cocaine, diazepam, drug interaction, fentanyl, gamma hydroxybutyrate, intravenous administration, naltrexone, self medication
Macaca mulatta, behavioral /social science research tag

Institution: UNIVERSITY OF MICHIGAN AT ANN ARBOR
3003 SOUTH STATE STREET, Room 1040
ANN ARBOR, MI 481091274
Fiscal Year: 2006
Department: PHARMACOLOGY
Project Start: 01-MAY-2003
Project End: 30-APR-2008
ICD: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
IRG: ALTX

J Exp Anal Behav. 2006 September; 86(2): 181195.
doi: 10.1901/jeab.2006.108.05.
PMCID: PMC1592359
Copyright Society for the Experimental Analysis of Behavior, Inc.

Assessing Unit-Price Related Remifentanil Choice in Rhesus Monkeys

Chad M Galuska, Gail Winger, and James H Woods

The subjects were 3 adult rhesus monkeys (Macaca mulatta), 2 male (Monkeys 3572 and 3603) and 1 female (Monkey 3600), with a history of drug self-administration including remifentanil. Monkeys lived in the experimental chambers and were fed 10 to 15 Purina monkey chow biscuits twice daily (at least 1.5 hr before experimental sessions) to maintain their body weights. Daily fresh fruit and other treats supplemented this diet. Water was continuously available. In accordance with institutional animal care and use requirements, environmental enrichment toys also were provided on a regular rotating basis.

Apparatus

Monkeys were permanently housed in stainless steel cages (83.3-cm long by 76.2-cm wide by 91.4-cm deep). The front, top, and bottom of the cage were made of barred stainless steel, and a pan was located below the floor to collect waste. Located on the wall to the left of the barred front door was an intelligence panel 20 cm in length and 15.4 cm in height, approximately 10 cm from the front and 19 cm from the bottom of the cage. Across the top of the stimulus panel, 1.5 cm apart, were three circular openings, 2.5 cm in diameter, covered with translucent plastic and capable of being illuminated from behind with 5-W colored bulbs. The two side lights could be illuminated red and the center light green. Centered below the right and left stimulus lights were response levers (Model 121-07, BRS-LVE) capable of being operated by 10 to 15 g (0.100.15 N) of force. A 0.3-cm thick stainless steel divider, centered between the response levers and below the stimulus lights, extended 8 cm into the chamber. Experimental control was provided by an IBM PS/2 computer located in an adjoining room and programmed with Med-PC (Med-Associates, Georgia, VT) software.
 
Each monkey wore a Teflon mesh jacket (Lomir, Quebec, Canada) connected to a flexible stainless-steel spring tether attached to the rear of the cage. Monkeys had been implanted previously with indwelling intravenous catheters in an internal or external jugular, or femoral vein, under ketamine (10 mg/kg, IM) and xylazine (2 mg/kg, IM) anesthesia. Catheters were run subcutaneously from the site of implantation to an exit site in the middle of the back. Tubing was then fed through the steel spring tether and passed to the outside rear of the cage where it was connected to a stock solution of remifentanil (either 0.4 g/kg/ml or 1.2 g/kg/ml) and additional infusion lines that passed through the rollers of two infusion pumps. Different doses were arranged by manipulating the speed of the two pumps. Operation of one pump delivered 0.15 ml solution per s. Operation of the other delivered 0.05 ml solution per s. Injections were always 5 s in duration. When the stock solution was 0.4 g/kg/ml remifentanil, operation of the faster pump resulted in a delivery of 0.3 g/kg/inj (0.4 g/kg/ml 0.15 ml/s 5 s) and operation of the slower pump delivered 0.1 g/kg/inj. When the stock solution was prepared at 1.2 g/kg/ml, doses of 0.9 and 0.3 g/kg/inj were arranged.

Please email:  GAIL D. WINGER, gwinger@umich.edu to protest the inhumane use of animals in this experiment. We would also love to know about your efforts with this cause: saen@saenonline.org

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Rats, mice, birds, amphibians and other animals have been excluded from coverage by the Animal Welfare Act. Therefore research facility reports do not include these animals. As a result of this situation, a blank report, or one with few animals listed, does not mean that a facility has not performed experiments on non-reportable animals. A blank form does mean that the facility in question has not used covered animals (primates, dogs, cats, rabbits, guinea pigs, hamsters, pigs, sheep, goats, etc.). Rats and mice alone are believed to comprise over 90% of the animals used in experimentation. Therefore the majority of animals used at research facilities are not even counted.

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