Journal article
Decreases in Endogenous Opioid Peptides in the Rat Medullo-Coerulear Pathway after Chronic Morphine Treatment
The Journal of neuroscience, v 20(23), pp 8659-8666
01 Dec 2000
PMID: 11102471
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Several biochemical changes have been described in noradrenergic neurons of the locus coeruleus (LC) after chronic morphine treatment. Changes in neurochemical expression in opioid afferent projections to the LC may be equally important in modulating noradrenergic neurons during chronic opiate exposure. To test the hypothesis that opioid peptides in LC afferents are altered after chronic opiate administration, we exposed adult male rats to either morphine or placebo pellets for 5 d. Tissue sections through the LC were processed for peroxidase or gold–silver labeling of methionine
5
-enkephalin (met-ENK) and analyzed using light or electron microscopy, respectively. Light level densitometry and ultrastructural analysis showed that there was a significant decrease in immunolabeling for ENK in LC-afferent terminals of morphine-treated rats. Western immunoblot analysis confirmed that protein levels for both leucine
5
- and methionine
5
-ENK were significantly decreased in tissue samples containing the LC after chronic morphine treatment. To test whether decreases in ENK protein expression were mirrored by decreases in gene expression, Northern blot analysis of preproenkephalin (PPE) mRNA was conducted in tissue samples obtained through the medulla, a brainstem area that contains the major opioid afferents to the LC. PPE mRNA was reduced in samples obtained from morphine-treated rats. Finally,
in situ
hybridization experiments confirmed significant decreases in PPE mRNA expression in the nucleus paragigantocellularis, a region known to provide a robust opioid input to the LC. These data suggest that there is a decrease in the synthesis of the opioid peptide mRNA and protein in the medullo-coerulear pathway after chronic exposure to morphine. Such alterations in opioid peptide levels during opiate dependence may contribute to the observed hyperactivity of LC neurons during opiate withdrawal.
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Details
- Title
- Decreases in Endogenous Opioid Peptides in the Rat Medullo-Coerulear Pathway after Chronic Morphine Treatment
- Creators
- Elisabeth J. Van Bockstaele - Thomas Jefferson UniversityJames Peoples - Thomas Jefferson UniversityA. Sue Menko - Thomas Jefferson UniversityKirk McHugh - Thomas Jefferson UniversityGuy Drolet - Université Laval
- Publication Details
- The Journal of neuroscience, v 20(23), pp 8659-8666
- Publisher
- Society for Neuroscience
- Number of pages
- 8
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000165592000018
- Scopus ID
- 2-s2.0-0034551765
- Other Identifier
- 991021903286704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences