Localization of endogenous morphine-like compounds in the mouse spinal cord

J Comp Neurol. 2012 May 1;520(7):1547-61. doi: 10.1002/cne.22811.


Morphine, codeine, morphine-6-glucuronide, and morphine-3-glucuronide are synthesized de novo in mammalian cells and in the central nervous system. Knowledge on endogenous morphine-like compound distribution in the adult mouse brain has been recently improved, and new hypotheses have been suggested about the potential implications in brain physiology. Endogenous morphine-like compounds have been shown to be synthesized in the spinal cord, but their localization is unknown. Here we describe the distribution of endogenous morphine-like compounds (morphine and/or its glucuronides and/or codeine) in the adult mouse spinal cord using a well-validated antibody. By using different microscopy approaches, we found the presence of morphine, codeine, or morphine glucuronides in γ-aminobutyric acid (GABA)-ergic neurons and astrocytes of the spinal cord. Whereas GABAergic neurons containing endogenous morphine-like compounds were located primarily in the ventral horn, astrocytes that were labeled for morphine-like compounds were found throughout the gray matter and the white matter. Our study demonstrates the possibility that endogenous morphine-like compounds in the central nervous system have other functions beyond their analgesic functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Codeine / analysis
  • Codeine / biosynthesis
  • GABAergic Neurons / metabolism*
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Morphine / analysis
  • Morphine / biosynthesis
  • Morphine Derivatives / analysis*
  • Morphine Derivatives / metabolism
  • Spinal Cord / metabolism*


  • Morphine Derivatives
  • morphine-6-glucuronide
  • Morphine
  • morphine-3-glucuronide
  • Codeine