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PMID:16194531

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Citation

Drake, CT, Aicher, SA, Montalmant, FL and Milner, TA (2005) Redistribution of mu-opioid receptors in C1 adrenergic neurons following chronic administration of morphine. Exp. Neurol. 196:365-72

Abstract

Neurons in the rostral ventrolateral medulla (RVLM) are involved in both tonic and reflex control of sympathetic outflow. Many of these neurons express the adrenaline-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT), and are designated C1 neurons. C1 neurons that contain mu-opioid receptors (MORs) are hyperpolarized by MOR activation and are activated during morphine withdrawal. The present study examined the subcellular distribution of the cloned MOR, MOR1, in rat C1 neurons following chronic morphine treatment, using RVLM sections that were dually labeled for PNMT-immunoperoxidase and MOR1-immunogold. Electron microscopic analysis of the subcellular distribution of MOR1 revealed a lower abundance of plasma membrane-associated MOR1 in C1 dendrites of rats treated with morphine, compared to placebo-treated controls, only in distal dendrites. There were no differences in the size of dual-labeled dendrites between treatment groups or in the overall density of MOR1 within PNMT immunoreactive dendrites between treatment groups. These results suggest that chronic morphine treatment leads to a decreased presence of MOR1 at the cell surface, without a significant reduction in cytoplasmic receptor density. These observations suggest that chronic morphine produces a selective internalization of MOR1 in C1 neurons, without apparent changes in receptor synthesis or trafficking. The reduction of accessible MORs on these neurons may be a mechanism for tolerance with regard to autonomic responses to opioid administration and may facilitate the profound sympathetic hyperactivity that occurs during acute opioid withdrawal.

Links

PubMed Online version:10.1016/j.expneurol.2005.08.012

Keywords

Animals; Behavior, Animal; Dendrites/drug effects; Dendrites/ultrastructure; Drug Administration Schedule; Male; Medulla Oblongata/cytology; Microscopy, Immunoelectron/methods; Morphine/administration & dosage; Narcotics/administration & dosage; Neurons/drug effects; Neurons/metabolism; Neurons/ultrastructure; Pain Measurement/methods; Phosphatidylethanolamine N-Methyltransferase/metabolism; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:OPRM

located_in

GO:0032590: dendrite membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:OPRM

located_in

GO:0032839: dendrite cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:OPRM

part_of

GO:0032590: dendrite membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:OPRM

part_of

GO:0032839: dendrite cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:OPRM

involved_in

GO:0043278: response to morphine

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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