μ‐Opioid Receptor Redistribution in the Locus Coeruleus Upon Precipitation of Withdrawal in Opiate‐Dependent Rats
Year: 2009
Type: article
Abstract: Administration of mu-opioid receptor (MOR) agonists is known to produce adaptive changes within noradrenergic neurons of the rat locus coeruleus (LC). Alterations in the subcellular distribution of MOR have been shown to occur in the LC in response to full agonists and endogenous peptides; however, there is considerable debate in the literature whether trafficking of MOR occurs after chronic exposure to the partial-agonist morphine. In the present study, we examined adaptations in MOR after chronic opioid exposure using immunofluorescence and electron microscopy (EM), using receptor internalization as a functional endpoint. MOR trafficking in LC neurons was characterized in morphine-dependent rats that were given naltrexone at a dose known to precipitate withdrawal. After chronic morphine exposure, a subtle redistribution of MOR immunoreactivity from the membrane to the cytosol was detected within dendrites of LC neurons. Interestingly, an acute injection of naltrexone in rats exposed to chronic morphine produced a robust internalization of MOR, whereas administration of naltrexone failed to do so in naïve animals. These findings provide anatomical evidence for modified regulation of MOR trafficking after chronic morphine treatment in brain noradrenergic neurons. Adaptations in the MOR signaling pathways that regulate internalization may occur as a consequence of chronic treatment and precipitation of withdrawal. Mechanisms underlying this effect might include differential MOR regulation in the LC, or downstream effects of withdrawal-induced enkephalin (ENK) release from afferents to the LC.
Source: The Anatomical Record
DOI: 10.1002/ar.20860
Institution: Thomas Jefferson University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Awards: G1292995420, G2017012497, G2391500998, Opioid modulation of the coeruleo-cortical pathway, G5163458049, Very Low Naltrexone Treatment of Opiate Withdrawal, Opioids, Stress and Noradrenergic Neurons, Confocal Core Facility for Vision Researchers, Cannabinoid and Cpioid Interactions in Noradrenergic Cells, G96377584
OpenAlex ID: W2003935296