McLean Hospital, Belmont, MA

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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

McLean Hospital, Belmont, MA

CAROL A. PARONIS - Primate Testing - 2006

Grant Number: 5R01DA015723-03
Project Title: Opioids:Relative Reinforcing Strength and Dependence
PI Information: ASSISTANT PROFESSOR CAROL A. PARONIS, cparonis@hms.harvard.edu 

Abstract: DESCRIPTION (provided by applicant):
Considerable effort has been dedicated to understanding physiological and behavioral aspects of opioid dependence, yet little is known regarding how opioid dependence alters the reinforcing effects of heroin. Since 1968, when it was first demonstrated that prior dependence is not required for animals to initiate self-administration of abused drugs, very few studies have examined self-administration behavior in opioid-dependent subjects. The proposed research is designed to address questions of whether and how reinforcing effects of opioids are altered as a function of dependence, including dependence that results from identified pharmacotherapies for heroin addiction, e.g., buprenorphine. We have developed innovative self-administration procedures in which full dose-effect functions for the relative reinforcing strength of IV heroin can be rapidly determined. In these novel choice procedures, subjects learn to distribute their behavior throughout the session on the basis of the relative reinforcing strong features of an IV solution that is available for self-injection and an alternative reinforcer (food). These procedures are especially designed to divorce the reinforcing strength of drugs from other behavioral effects. In proposed studies, the self-administration of heroin and other opioid agonists will be determined under varying conditions of response cost to evaluate contextual influences on relative reinforcing strength. Next, studies will be conducted to determine how the relative reinforcing strength of heroin is modulated by acute treatment and chronic treatment with morphine-like drugs. Preliminary data indicate that the reinforcing strength of heroin in nondependent subjects can be predictably altered by treatment with other opioids or by changes in response cost, confirming the utility of these procedures for studies of the relative reinforcing strength of self-administered heroin. Following completion of these studies, alteration in the reinforcing strength of heroin will be gauged in relation to aspects of tolerance and dependence that develop during chronic treatment. Lastly, planned experiments will address the modification of heroin's reinforcing effects by nonopioid drugs, specifically GABA-A agonists. These studies are designed to empirically address questions raised by high rates of benzodiazepine abuse by opioid-addicted populations. Overall, the proposed studies will provide significant advances for evaluating contextual or pharmacological modifications of the reinforcing strength of heroin in nondependent and opioid-dependent individuals. Results of these studies will improve our ability to assess the effectiveness with which agonist-based medications may combat its addictive power.

Thesaurus Terms:
drug addiction, heroin, opiate alkaloid, psychopharmacology, reinforcer
benzodiazepine, buprenorphine, disease /therapy duration, dosage, drug abuse chemotherapy, drug habituation, drug tolerance, gamma aminobutyrate, intravenous administration, intravenous drug abuse, narcotic antagonist, neurotransmitter agonist, self medication, substance abuse related behavior
Macaca mulatta, behavioral /social science research tag

Institution: MC LEAN HOSPITAL (BELMONT, MA)
115 MILL ST
BELMONT, MA 02478
Fiscal Year: 2006
Department:
Project Start: 14-MAY-2004
Project End: 31-MAR-2009
ICD: NATIONAL INSTITUTE ON DRUG ABUSE
IRG: BRLE

Journal of Pharmacology And Experimental Therapeutics Fast Forward

First published on October 16, 2003; DOI: 10.1124/jpet.103.052795

Modification by Dopaminergic Drugs of Choice Behavior under Concurrent Schedules of Intravenous Saline and Food Delivery in Monkeys
 
Maciej Gasior, Carol A. Paronis, and Jack Bergman
Behavioral Pharmacology Laboratory/Alcohol and Drug Abuse Research Center, McLean Hospital, Belmont, Massachusetts
Received April 8, 2003; accepted September 25, 2003.

Subjects.
Three female (Mm 211, Mm 258, and Mm 331) and one male (Mm 263) adult rhesus monkeys (Macaca mulatta), weighing 6 to 9.5 kg, were studied in daily experimental sessions 5 to 6 days/week. Two monkeys (Mm 211 and Mm 331) were previously exposed to cocaine in i.v. self-administration experiments, and two monkeys (Mm 258 and Mm 263) had previously participated in experiments with a variety of opioid or dopaminergic drugs. Subjects were individually housed in stainless steel cages between experimental sessions in a temperature- and humidity-controlled room with a 12-h light/dark cycle (7:00 AM lights on). Each monkey had unlimited access to tap water and received a nutritionally balanced diet (5045 High Protein Monkey Diet; PMI Nutrition International, Inc., Brentwood, MO) supplemented regularly with fresh fruit, trail mix, and vitamins. The protocol for animal use in these studies was approved by the Institutional Animal Care and Use Committee. Subjects in this study were maintained in accordance with guidelines provided by the Committee on Care and Use of Laboratory Animals of the Institute of Laboratory Animals Resources, National Institutes of Health. This facility is licensed by the U.S. Department of Agriculture.

Each monkey initially was trained to lever press under a fixed ratio schedule of food presentation. After food-maintained performance was well established, each monkey was prepared with a chronic venous catheter after the general surgical procedure described by Herd et al. (1969 ). Briefly, under isoflurane anesthesia and in aseptic conditions, one end of a hydrophilically coated polyurethane catheter (inside diameter, 1.0 mm; outside diameter, 1.7 mm) was inserted through a femoral vein and passed to the level of the right atrium. The distal end of the catheter was attached to a titanium vascular access port (model TI200 AC-5H; Access Technologies, Skokie, IL) that was subcutaneously located in the midscapular region.

Apparatus.
During experimental sessions, each monkey was seated in a Plexiglas chair within a ventilated, sound-attenuating chamber. Two response levers were mounted on a panel attached to the front of the chair. Each press of either lever with a force of at least 0.25 N produced an audible click of a relay and was recorded as a response. Colored lamps (red or white) behind the levers could be illuminated to serve as visual stimuli. A motor-driven feeder outside the chamber could deliver food pellets to a food receptacle on the chair via flexible tubing. A motor-driven syringe pump outside the chamber could deliver intravenous injections via an external catheter line and noncoring Huber needle through the silicone rubber septum of the monkey's vascular access port. Sterile 0.9% saline (1-2 ml) was used to flush residual drug solution from the port and catheter after experimental sessions. Both the syringe and feeder were operated by automatic programming equipment. Each operation of the syringe pump or feeder lasted 200 ms and delivered a constant volume from the syringe or one food pellet, respectively.

 

Please email: CAROL A. PARONIS, cparonis@hms.harvard.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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