Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance.

Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance. Abstract Text:

L J Sim-Selley,K L Scoggins,M P Cassidy,L A Smith,W L Dewey,F L Smith,D E Selley,

BACKGROUND AND PURPOSE: Chronic morphine administration produces tolerance in vivo and attenuation of mu opioid receptor (MOR)-mediated G-protein activation measured in vitro, but the relationship between these adaptations is not clear. The present study examined MOR-mediated G-protein activation in the CNS of mice with different levels of morphine tolerance. EXPERIMENTAL APPROACH: Mice were implanted with morphine pellets, with or without supplemental morphine injections, to induce differing levels of tolerance as determined by a range of MOR-mediated behaviours. MOR function was measured using agonist-stimulated [(35)S]guanylyl-5'-O-(gamma-thio)-triphosphate ([(35)S]GTPgammaS) and receptor binding throughout the CNS. KEY RESULTS: Morphine pellet implantation produced 6-12-fold tolerance in antinociceptive assays, hypothermia and Straub tail, as measured by the ratio of morphine ED(50) values between morphine-treated and control groups. Pellet implantation plus supplemental injections produced 25-50-fold tolerance in these tests. In morphine pellet-implanted mice, MOR-stimulated [(35)S]GTPgammaS binding was significantly reduced only in the nucleus tractus solitarius (NTS) and spinal cord dorsal horn in tissue sections from morphine pellet-implanted mice. In contrast, MOR-stimulated [(35)S]GTPgammaS binding was significantly decreased in most regions examined in morphine pellet+morphine injected mice, including nucleus accumbens, caudate-putamen, periaqueductal gray, parabrachial nucleus, NTS and spinal cord. CONCLUSIONS AND IMPLICATIONS: Tolerance and the regional pattern of apparent MOR desensitization were influenced positively by the level of morphine exposure. These results indicate that desensitization of MOR-mediated G-protein activity is more regionally widespread upon induction of high levels of tolerance, suggesting that this response contributes more to high than low levels of tolerance to CNS-mediated effects of morphine.

Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance. Publishing Authors By Initials

LJ Sim-Selley,KL Scoggins,MP Cassidy,LA Smith,WL Dewey,FL Smith,DE Selley,

For similar animal structures: tail research abstracts see: animal structures: tail research

PUBMED ID PMID:

MEDLINE DATE:

Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: British journal of pharmacology

VOLUME: 151

Page Numbers: 1324-33

Journal Abbreviation: Br. J. Pharmacol.

ISSN: 0007-1188

DAY: 18

MONTH: 06

YEAR: 2007

Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7502536

Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance. Keywords Mesh Terms:

KEYWORDS: Tail

MESH TERMS: drug effects

Chemical & Substance for Abstract: Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance. Information

Substance Name: GTP-Binding Proteins

Registry Number: EC 3.6.1.-

Grant and Affiliation Information for Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance.

AFFILIATION: Department of Pharmacology and Toxicology, Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Medical College of Virginia Campus, 1112 East Clay Street, Richmond, VA 23298, USA.

Country: England

AGENCY: United States NIDA

GRANT: DA 10770

ACRONYM: DA

MEDLINETA: Br J Pharmacol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance Related Publications

• A metabolic link between S-adenosylhomocysteine and polyunsaturated fatty acid metabolism in Alzheimer's disease.
• Hazards of sulphinpyrazone.
• Region-dependent attenuation of mu opioid receptor-mediated G-protein activation in mouse CNS as a function of morphine tolerance.
• Remedy for excessive salivation.