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Sex differences in morphine-induced trafficking of mu-opioid and corticotropin-releasing factor receptors in locus coeruleus neurons
Journal article   Peer reviewed

Sex differences in morphine-induced trafficking of mu-opioid and corticotropin-releasing factor receptors in locus coeruleus neurons

Nicole M Enman, Beverly A S Reyes, Yufan Shi, Rita J Valentino and Elisabeth J Van Bockstaele
Brain research, v 1706, pp 75-85
01 Mar 2019
DOI: https://doi.org/10.1016/j.brainres.2018.11.001
PMID: 30391476
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Analgesics, Opioid - pharmacology Animals Corticotropin-Releasing Hormone - metabolism Female Locus Coeruleus - drug effects Male Microscopy, Immunoelectron - methods Morphine - pharmacology Neurons - drug effects Neurons - metabolism Norepinephrine - metabolism Opioid Peptides - metabolism Protein Transport - drug effects Rats Rats, Sprague-Dawley Receptors, Corticotropin-Releasing Hormone - drug effects Receptors, Corticotropin-Releasing Hormone - metabolism Receptors, Opioid, mu - drug effects Receptors, Opioid, mu - metabolism Rhombencephalon - drug effects Sex Characteristics Sex Factors Stress, Physiological - physiology
The locus coeruleus (LC)-norepinephrine (NE) system is a key nucleus in which endogenous opioid and stress systems intersect to regulate the stress response. LC neurons of male rats become sensitized to stress following chronic morphine administration. Whether sex dictates this pattern of opioid-induced plasticity has not been demonstrated. Delineating the neurobiological adaptations produced by chronic opioids will enhance our understanding of stress vulnerability in opioid-dependent individuals, and may reveal how stress negatively impacts addiction recovery. In the present study, the effect of chronic morphine on the subcellular distribution of mu-opioid (MOR) and CRF receptors (CRFR) was investigated in the LC of male and female rats using immunoelectron microscopy. Results showed that placebo-treated females exhibited higher MOR and CRFR cytoplasmic distribution ratio when compared to placebo-treated males. Chronic morphine exposure induced a shift in the distribution of MOR immunogold-silver particles from the plasma membrane to the cytoplasm selectively in male LC neurons. Interestingly, chronic morphine exposure induced CRFR recruitment to the plasma membrane of both male and female LC neurons. These findings provide a potential mechanism by which chronic opioid administration increases stress vulnerability in males and females via an increase in surface availability of CRFR in LC neurons. However, our results also support the notion that cellular adaptations to chronic opioids differ across the sexes as redistribution of MOR following morphine exposure was only observed in male LC neurons.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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