NDLI: Attenuation of morphine tolerance after antisense oligonucleotide knock-down of spinal mGluR1

Content Provider	PubMed Central
Author	Sharif, Reza N. Osborne, Michael Coderre, Terence J. Fundytus, Marian E.
Copyright Year	2002
Abstract	Chronic systemic treatment of rats with morphine leads to the development of opioid tolerance. This study was designed to examine the effects of intrathecal (i.t.) infusion of a metabotropic glutamate receptor 1 (mGluR1) antisense oligonucleotide, concomitant with chronic morphine treatment, on the development of tolerance to morphine's antinociceptive effects. All rats received chronic (6 day) s.c. administration of morphine to induce opioid tolerance. Additionally, rats were treated with either mGluR1 antisense (AS), missense (MIS) or artificial cerebrospinal fluid (ACSF) by i.t. infusion via chronically implanted i.t. catheters connected to osmotic mini-pumps. The effects of acute i.t. or s.c. morphine on tail-flick latencies were assessed prior to and following chronic s.c. morphine treatment for all chronic i.t. infusion groups. mGluR1 protein level in the spinal cord was determined by Western blot analysis for all treatments, assessing the efficiency of knock-down with AS treatment. Acute i.t. morphine dose-dependently produced antinociception in the tail-flick test in naïve rats. Systemic morphine-treated rats administered i.t. ACSF or MIS developed tolerance to i.t. morphine. Chronic i.t. infusion with mGluR1 AS significantly reduced the development of tolerance to i.t. morphine. In contrast to i.t. morphine, tolerance developed to the antinociceptive effects of s.c. morphine, in all i.t. infusion groups, including the mGluR1 AS group. The spinal mGluR1 protein level was dramatically decreased after mGluR1 AS infusion when compared to control animals (naïve and ACSF-treated animals). These findings suggest that the spinal mGluR1 is involved in the development of tolerance to the antinociceptive effects of morphine. Selective blockade of mGluR1 may be beneficial in preventing the development of opioid analgesic tolerance.
Related Links	http://dx.doi.org/10.1038/sj.bjp.0704792
Ending Page	872
Page Count	8
Starting Page	865
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	6
Volume Number	136
Language	English
Publisher Date	2002-07-01
Access Restriction	Open
Subject Keyword	Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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