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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 Texas at San Antonio, San Antonio, TX
CHARLES P. FRANCE - Primate Testing - 2006
Grant Number: 5R01DA005018-20
Project Title: Discriminative stimulus effects of opioid
withdrawal
PI Information: PROFESSOR CHARLES P. FRANCE,
[email protected]
Abstract: DESCRIPTION (provided by applicant): Opioid abuse
remains a significant public health problem despite continued research
and the availability of new drugs for treatment. In addition to the
ongoing problem of heroin abuse is a growing concern about the
recreational use of potent, efficacious opioid analgesics such as
oxycodone. This is a competing continuation of a grant that has
developed novel drug discrimination procedures for studying opioid
dependence and withdrawal; those procedures have been used in concert
with other measures of opioid activity to examine a range of
pharmacologic and behavioral parameters that contribute to the abuse and
dependence liability of morphine and related opioids. Studies proposed
in this renewal exploit these discrimination procedures to focus on the
neuropharmacology of opioid dependence and withdrawal as well as the
role of opioid withdrawal in drug taking. AIM I characterizes the
neuropharmacology of opioid withdrawal in rhesus monkeys by examining
monoaminergic drugs for their ability to modulate discriminative
stimulus and other effects (directly observable and HPA activation) of
opioid withdrawal in monkeys. These studies build upon published data
from this laboratory showing that dopamine uptake blockers attenuate
discriminative stimulus and not other indices of withdrawal. AIM II
combines a well-established drug discrimination procedure with i.v. self
administration in monkeys to examine the effects of withdrawal on self
administration of cocaine and mu agonists that vary in efficacy. AIM III
provides a comprehensive set of descriptive data from rhesus monkeys on
the behavioral pharmacology of several prescription opioids that are
believed to be increasingly abused, including oxycodone, oxymorphone,
hydrocodone and hydromorphone. While it is assumed that these opioids
have exclusively morphine-like actions, there are limited data available
to support that view. The four opioids will be compared to morphine
using measures of drug discrimination, antinociception, and respiration.
Finally, studies under AIM IV investigate the relationship between
opioid tolerance and dependence, on the one hand, and constitutive
activity and inverse agonism at opioid receptors, on the other hand,
using drug discrimination procedures in pigeons with varying degrees of
morphine tolerance and dependence. These studies should provide insight
to the lasting neurobiological changes that can occur as a consequence
of chronic drug treatment. Collectively these studies will apply drug
discrimination and other procedures to important question regarding
opioid dependence, withdrawal and abuse and will provide information
that will facilitate the development of new therapeutics for opioid
abuse.
Thesaurus Terms:
discrimination learning, drug withdrawal, neuropharmacology, opiate
alkaloid, psychopharmacology, substance abuse related behavior
dopamine transporter, drug habituation, drug tolerance, ligand,
naltrexone, neuroendocrine system, opioid receptor, pharmacokinetics,
self medication
Macaca mulatta, behavioral /social science research tag, pigeon
Institution: UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT
SAN ANTONIO, TX 78229
Fiscal Year: 2006
Department: PHARMACOLOGY
Project Start: 01-MAY-1995
Project End: 30-JUN-2008
ICD: NATIONAL INSTITUTE ON DRUG ABUSE
IRG: ZRG1
Efficacy and the Discriminative Stimulus Effects of
Negative GABAA Modulators, or Inverse Agonists, in Diazepam-Treated
Rhesus Monkeys
Lance R. McMahon, Lisa R. Gerak, and Charles P. France
Departments of Pharmacology (L.R.M., L.R.G., C.P.F.) and Psychiatry (C.P.F.),
the University of Texas Health Science Center at San Antonio, San
Antonio, Texas
Received February 17, 2006; accepted May 15, 2006.
JPET 318:907-913, 2006
Subjects. One female and five male adult rhesus monkeys were
housed individually on a 14-h light/10-h dark schedule, were maintained
at 95% free-feeding weight (range 8.0-11 kg) with a diet comprising
primate chow (Harlan Teklad, High Protein Monkey Diet; Harlan Teklad,
Madison, WI), fresh fruit, and peanuts, and were provided water in the
home cage. Monkeys received 5.6 mg/kg/day diazepam, were trained to
discriminate flumazenil, and had received GABAA ligands in previous
studies (McMahon and France, 2005 ). The animals used in these studies
were maintained in accordance with the Institutional Animal Care and Use
Committee, The University of Texas Health Science Center at San Antonio,
San Antonio, TX, and with the 1996 Guide for the Care and Use of
Laboratory Animals (Institute of Laboratory Animal Resources on Life
Sciences, National Research Council, National Academy of Sciences).
Apparatus. During experimental sessions, monkeys were seated in
chairs (model R001; Primate Products, Miami, FL) that provided restraint
at the neck and were placed in ventilated, sound-attenuating chambers
equipped with two response levers, stimulus lights, and a food cup to
which pellets (Bio-Serv, Frenchtown, NJ) could be delivered from a
dispenser. An interface (MedAssociates, St. Albans, VT) connected the
chambers to a computer that controlled and recorded experimental events.
Discrimination Procedure. Monkeys drank a solution containing
diazepam (5.6 mg/kg) 3 h before experimental sessions consisting of
multiple 15-min cycles. Each cycle comprised a 10-min timeout period,
during which responses had no programmed consequence, followed by a
5-min response period, during which green stimulus lights were
illuminated and a fixed ratio (FR) 5 schedule of food presentation was
in effect. A maximum of 10 food pellets was available during a cycle;
when the maximal number of food pellets was obtained in <5 min, the
remainder of the response period was a timeout. The selection of
vehicle- and flumazenil-appropriate levers varied among monkeys and
remained the same for an individual throughout the study. Responding on
the incorrect lever reset the response requirement on the correct lever. |
Please email: CHARLES P.
FRANCE, [email protected]
to protest the inhumane use of animals in this
experiment. We would also love to know about your efforts with this
cause:
[email protected]
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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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