The cannabinoid receptor agonist, WIN 55,212-2, inhibits cool-specific lamina I medullary dorsal horn neurons

Neuroscience. 2006 Nov 17;143(1):265-72. doi: 10.1016/j.neuroscience.2006.07.040. Epub 2006 Sep 1.

Abstract

Cannabinoid receptor agonists have been demonstrated to inhibit medullary and spinal cord dorsal horn nociceptive neurons. The effect of cannabinoids on thermoreceptive specific neurons in the spinal or medullary dorsal horn remains unknown. In the present study, single-unit recordings from the rat medullary dorsal horn were performed to examine the effect of a cannabinoid receptor agonists on cold-specific lamina I spinothalamic tract neurons. The cannabinoid CB1/CB2 receptor agonist, WIN 55,212-2 (WIN-2), was locally applied to the medullary dorsal horn and the neuronal activity evoked by cooling the receptive field was recorded. WIN-2 (1 microg/microl and 2 microg/microl) significantly attenuated cold-evoked activity. Co-administration of the CB1 receptor antagonist SR 141716 with WIN-2 did not affect cold-evoked activity. These results demonstrate a potential mechanism by which cannabinoids produce hypothermia, and also suggest that cannabinoids may affect non-noxious thermal discrimination.

Publication types

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

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Action Potentials / radiation effects
  • Analysis of Variance
  • Animals
  • Benzoxazines
  • Cannabinoid Receptor Agonists*
  • Cannabinoid Receptor Antagonists
  • Cold Temperature
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electric Stimulation / methods
  • Male
  • Morpholines / pharmacology*
  • Naphthalenes / pharmacology*
  • Neural Inhibition / drug effects*
  • Neural Inhibition / physiology
  • Neural Inhibition / radiation effects
  • Piperidines / pharmacology
  • Posterior Horn Cells / drug effects*
  • Posterior Horn Cells / physiology
  • Posterior Horn Cells / radiation effects
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Rimonabant
  • Spinal Cord / cytology*

Substances

  • Benzoxazines
  • Cannabinoid Receptor Agonists
  • Cannabinoid Receptor Antagonists
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Rimonabant