Distribution of CB1 cannabinoid receptors and their relationship with mu-opioid receptors in the rat periaqueductal gray

Neuroscience. 2012 Jun 28;213:191-200. doi: 10.1016/j.neuroscience.2012.03.038. Epub 2012 Apr 19.


The periaqueductal gray (PAG) is part of a descending pain modulatory system that, when activated, produces widespread and profound antinociception. Microinjection of either opioids or cannabinoids into the PAG elicits antinociception. Moreover, microinjection of the cannabinoid 1 (CB1) receptor agonist HU-210 into the PAG enhances the antinociceptive effect of subsequent morphine injections, indicating a direct relationship between these two systems. The objective of this study was to characterize the distribution of CB1 receptors in the dorsolateral and ventrolateral PAG in relationship to mu-opioid peptide (MOP) receptors. Immunocytochemical analysis revealed extensive and diffuse CB1 receptor labeling in the PAG, 60% of which was found in somatodendritic profiles. CB1 and MOP receptor immunolabeling were co-localized in 32% of fluorescent Nissl-stained cells that were analyzed. Eight percent (8%) of PAG neurons that were MOP receptor-immunoreactive (-ir) received CB1 receptor-ir appositions. Ultrastructural analysis confirmed the presence of CB1 receptor-ir somata, dendrites and axon terminals in the PAG. These results indicate that behavioral interactions between cannabinoids and opioids may be the result of cellular adaptations within PAG neurons co-expressing CB1 and MOP receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Immunohistochemistry
  • Male
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Neurons / metabolism*
  • Neurons / ultrastructure*
  • Periaqueductal Gray / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / biosynthesis*
  • Receptors, Opioid, mu / biosynthesis*


  • Receptor, Cannabinoid, CB1
  • Receptors, Opioid, mu