Antinociception and delta-1 opioid receptors in the rat spinal cord: studies with intrathecal 7-benzylidenenaltrexone

Donna L Hammond; Peggy E Stewart; Larry Littell

doi:10.1016/S0022-3565(25)10651-4

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Antinociception and delta-1 opioid receptors in the rat spinal cord: studies with intrathecal 7-benzylidenenaltrexone

Journal article

Peer reviewed

Antinociception and delta-1 opioid receptors in the rat spinal cord: studies with intrathecal 7-benzylidenenaltrexone

Donna L Hammond, Peggy E Stewart and Larry Littell

The Journal of pharmacology and experimental therapeutics, Vol.274(3), pp.1317-1324

09/1995

DOI: 10.1016/S0022-3565(25)10651-4

PMID: 7562504

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Abstract

As part of the continuing investigation of the role of spinal delta opioid receptors in antinociception, this study characterized the ability of 7-benzylidenenaltrexone (BNTX), a selective delta-1 opioid receptor antagonist, to antagonize the antinociception produced in the rat by intrathecal (i.t.) administration of the respective delta-1 and delta-2 opioid receptor agonists, DPDPE and [D-Ala2, Glu4]deltorphin (DELT), or the mu receptor agonist DAMGO. In the tail flick test, 10-min pretreatment with 1 microgram of BNTX, increased the ED50 value of DPDPE from 27.5 micrograms (42.6 nmol) to 114.8 micrograms (177.8 nmol), but did not increase the ED50 values of either DELT or DAMGO. Increasing the dose of BNTX to 3 micrograms did not produce a significantly greater antagonism of the antinociceptive effects of DPDPE and did not antagonize the antinociceptive effects of DAMGO. However, it did enhance the antinociceptive effects of DELT decreasing its ED50 from 5.3 to 0.18 micrograms in the tail flick test. In the hot plate test, 10 min pretreatment with 1 microgram of BNTX selectively antagonized the antinociceptive effects of DPDPE, but did not antagonize the actions of DAMGO or DELT. Increasing the dose of BNTX to 3 micrograms also did not produce a significantly greater antagonism of the antinociceptive effects of DPDPE in the hot plate test, but did antagonize both the increase in hot plate latency and the modest decrement in motor function produced by 30 micrograms i.t. of DELT. However, the antagonism of these effects of DELT occurred much later in time than BNTX's antagonism of the antinociceptive effects of DPDPE.

Injections, Spinal

Naltrexone - analogs & derivatives

Analgesics - pharmacology

Narcotic Antagonists - administration & dosage

Spinal Cord - drug effects

Spinal Cord - metabolism

Analgesics - administration & dosage

Rats

Male

Rats, Sprague-Dawley

Enkephalin, D-Penicillamine (2,5)

Dose-Response Relationship, Drug

Naltrexone - pharmacology

Animals

Benzylidene Compounds - pharmacology

Narcotic Antagonists - pharmacology

Benzylidene Compounds - administration & dosage

Enkephalin, Ala-MePhe-Gly

Pain Threshold - drug effects

Receptors, Opioid, delta - antagonists & inhibitors

Enkephalins - pharmacology

Oligopeptides - pharmacology

Naltrexone - administration & dosage

Details

Title: Subtitle: Antinociception and delta-1 opioid receptors in the rat spinal cord: studies with intrathecal 7-benzylidenenaltrexone
Creators: Donna L Hammond - Department of Anesthesia and Critical Care, University of Chicago, Illinois, USA
Peggy E Stewart
Larry Littell
Resource Type: Journal article
Publication Details: The Journal of pharmacology and experimental therapeutics, Vol.274(3), pp.1317-1324
Publisher: United States
DOI: 10.1016/S0022-3565(25)10651-4
PMID: 7562504
ISSN: 0022-3565
eISSN: 1521-0103
Grant note: DA 06736 / NIDA NIH HHS
Language: English
Date published: 09/1995
Academic Unit: Iowa Neuroscience Institute; Nursing; Anesthesia; Neuroscience and Pharmacology
Record Identifier: 9984006314202771

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