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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 North Carolina, Chapel Hill, NC
LINDA A. DYKSTRA - Primate Testing - 2006
Grant Number: 5R01DA002749-29
Project Title: Opioid Analgesics: Pharmacological & Behavioral
Factors
PI Information: PROFESSOR LINDA A. DYKSTRA,
[email protected]
Abstract: DESCRIPTION (provided by applicant): There is growing
evidence that the N-methyl-D-aspartate (NMDA) class of the glutamate
receptor modulates the effects of a number of drugs of abuse. Therefore,
it is likely that a deeper understanding of interactions of the NMDA
system with drugs of abuse will inform the search for treatment
interventions, both in relationship to drug dependence and pain
modulation. The proposed experiments explore the mechanisms underlying
interactions between the NMDA system and opioid analgesics using an
integrative strategy that combines genetic, pharmacological and
behavioral approaches. The genetic approach employs an animal model of
NMDA deficiency that consists of partial deletion of the gene encoding
the essential NR1 subunit of the NMDA receptor (NR1-/- mice). The
pharmacological approach explores interactions between drugs of abuse
and a range of NMDA antagonists in mice of the C57BL/6 background
strain. Both the genetic and the pharmacological approaches are used to
investigate several prominent behavioral effects of opioid analgesics,
namely their antinociceptive, conditioned and reinforcing effects.
Specific Aim 1 examines the role of NMDA receptors in opioid
antinociception and tolerance, employing two different antinociceptive
assays: the hot plate procedure and the tail withdrawal procedure.
Specific Aim 2 investigates the role of NMDA receptors in the
conditioned effects of morphine and other opioid analgesics using the
conditioned place preference procedure (CPP) and Specific Aim 3
investigates in the reinforcing effects of opioid agonists using a drug
self-administration procedure. Preliminary experiments indicate the
feasibility of using these approaches in our own laboratory.
Collectively, the specific aims test the hypothesis that the
antinociceptive and reinforcing effects of morphine and other opioid
analgesics are altered in NR1-/- mice as compared to WT controls and
that morphine's effects are altered by the administration of selective
NMDA antagonists in two background strains of mice, C57BL/6 and 129/SvEv.
Public Health Relevance:
This Public Health Relevance is not available.
Thesaurus Terms:
NMDA receptor, analgesic, drug abuse, neuropharmacology, neuroregulation,
opiate alkaloid, protein structure function, psychopharmacology
conditioning, dextromethorphan, dizocilpine, drug tolerance, morphine,
neuropsychology, neurotransmitter antagonist, pain, reinforcer, self
medication animal genetic material tag, behavior test, genetically
modified animal, laboratory mouse
Institution: UNIVERSITY OF NORTH CAROLINA CHAPEL HILL
Office of Sponsored Research
CHAPEL HILL, NC 27599
Fiscal Year: 2006
Department: NONE
Project Start: 01-SEP-1977
Project End: 31-DEC-2009
ICD: NATIONAL INSTITUTE ON DRUG ABUSE
IRG: NMBVol. 300, Issue 2, 435-441, February
2002
Dextromethorphan Potentiates the Antinociceptive
Effects of Morphine and the -Opioid Agonist SNC80 in Squirrel Monkeys
Richard M. Allen, Arthur L. Granger and Linda A. Dykstra
Departments of Psychology (R.M.A., A.L.G., L.A.D.) and
Pharmacology (L.A.D.), University of North Carolina at Chapel Hill,
Chapel Hill, North Carolina
Animals.
Four adult male squirrel monkeys (Saimiri sciureus) weighing between
0.70 and 0.95 kg were housed in pairs in a colony room with a 12-h
light/dark cycle. All monkeys had continuous access to water, were
maintained on a high-protein monkey diet, and were given fresh fruit and
nuts daily. All of the monkeys had previous experience with the
titration procedure and had received various opioid compounds but had
not received drugs for at least 30 days before the start of the present
experiment.
Apparatus.
During experimental sessions, each monkey sat in a Plexiglas chair and
was held in place by a waist support with its tail secured by a small
stock (see Dykstra, 1985 ). The tail was coated with EKG Sol, a
noncorrosive electrode paste (Graphics Control Medical Products
Division, Buffalo, NY), to provide a low-resistance electrical contact.
Electric shock (110 V a.c., 60 Hz) was delivered through two hinged
brass plates that rested on a shaved portion of the tail.
Each chair was enclosed within a ventilated, sound-attenuating chamber
and was illuminated by a 10-W white houselight during experimental
sessions. A lever was mounted on the right side of the front panel, 8.5
cm above the waist plate and 4.0 cm from the right side wall. During
experimental sessions, presses on the lever with a downward force of
0.15 newton produced an audible click and were recorded as responses.
White noise was presented continuously both inside the chamber and
throughout the experimental room. Experimental events, including control
of shock intensity, were controlled using Med Associates software and
hardware (St. Albans, VT) through a microcomputer located in the
adjacent room.
Behavioral Procedure.
A shock titration procedure nearly identical to that described by
Dykstra (1985) was used. In each session, periods during which an FR 5
schedule of shock titration was in effect alternated with periods of
blackout. Each FR 5 titration period began with the illumination of the
house light and presentation of 0.01-mA shock. Shock intensity increased
from 0.01 to 2.0 mA in 30 increments. Completion of the FR 5 requirement
at a given shock intensity initiated a time-out during which shock was
off and the house light remained illuminated. After the 15-s time-out,
the shock resumed at the next lower intensity. If a monkey failed to
complete the FR 5 during 15 s at a given shock intensity, the intensity
increased by one increment and the response requirement was reset to 5.
The FR 5 titration periods usually lasted 15 min. An FR 5 period
terminated automatically, however, if the shock intensity rose to the
peak intensity of 2.0 mA and the FR 5 requirement was not completed
during any of five consecutive 15-s periods. During the blackouts that
separated the FR 5 titration periods, the chamber was dark, no shock was
delivered, and lever presses had no programmed consequences. Blackouts
lasted 20 min. Each session began with an FR 5 titration period and
ended after completion of five FR 5 periods.
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Please email: LINDA A.
DYKSTRA, [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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