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Chronic Morphine Reduces Surface Expression of δ-Opioid Receptors in Subregions of Rostral Striatum

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Abstract

The delta opioid receptor (DOPr), whilst not the primary target of clinically used opioids, is involved in development of opioid tolerance and addiction. There is growing evidence that DOPr trafficking is involved in drug addiction, e.g., a range of studies have shown increased plasma membrane DOPr insertion during chronic treatment with opioids. The present study used a transgenic mouse model in which the C-terminal of the DOPr is tagged with enhanced-green fluorescence protein to examine the effects of chronic morphine treatment on surface membrane expression in striatal cholinergic interneurons that are implicated in motivated learning following both chronic morphine and morphine sensitization treatment schedules in male mice. A sex difference was noted throughout the anterior striatum, which was most prominent in the nucleus accumbens core region. Incontrast with previous studies in other neurons, chronic exposure to a high dose of morphine for 6 days had no effect, or slightly decreased (anterior dorsolateral striatum) surface DOPr expression. A morphine sensitization schedule produced similar results with a significant decrease in surface DOPr expression in nucleus accumbens shell. These results suggest that chronic morphine and morphine sensitisation treatment may have effects on instrumental reward-seeking behaviours and learning processes related to drug addiction, via effects on striatal DOPr function.

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Acknowledgments

This work was supported by National Institute of Mental Health Grant MH56646, National Health and Medical Research Council Grant 633267 (B.W.B.), an Australian Laureate Fellowship from the Australian Research Council (B.W.B.), and a National Health and Medical Research Council Senior Principal Research Fellowship (M.J.C.). We thank Billy Chieng for assistance and Prof. Brigitte Kieffer for DOPr-eGFP knock-in mice.

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Authors and Affiliations

  1. Discipline of Pharmacology, University of Sydney, Sydney, NSW, 2006, Australia

    Paul M. Leah & Macdonald J. Christie

  2. Brain and Mind Research Institute, University of Sydney, Sydney, NSW, 2006, Australia

    Emily M. L. Heath & Bernard W. Balleine

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  1. Paul M. Leah
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  2. Emily M. L. Heath
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  3. Bernard W. Balleine
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  4. Macdonald J. Christie
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Correspondence to Macdonald J. Christie.

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Special Issue: In honor of Dr. Philip Beart.

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Leah, P.M., Heath, E.M.L., Balleine, B.W. et al. Chronic Morphine Reduces Surface Expression of δ-Opioid Receptors in Subregions of Rostral Striatum. Neurochem Res 41, 500–509 (2016). https://doi.org/10.1007/s11064-015-1638-6

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  • DOI: https://doi.org/10.1007/s11064-015-1638-6

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