Cannabinoid receptors are localized to noradrenergic axon terminals in the rat frontal cortex

Brain Res. 2007 Jan 5;1127(1):36-44. doi: 10.1016/j.brainres.2006.09.110. Epub 2006 Nov 17.


Cannabinoid agonists exert complex actions on modulatory neurotransmitters involved in attention and cognition. Previous studies have demonstrated that acute systemic administration of the synthetic cannabinoid agonist, WIN 55,212-2, increases norepinephrine efflux in the rat frontal cortex. In an effort to elucidate whether cannabinoid (CB1) receptors are positioned to presynaptically modulate norepinephrine release in the frontal cortex, immunocytochemical detection of the CB1 receptor and the catecholamine-synthesizing enzyme dopamine-beta-hydroxylase (DbetaH) was performed using confocal immunofluorescence microscopy and immunoelectron microscopy in rat brain. Fluorescence microscopy analysis of dually labeled tissue sections from the frontal cortex indicated that individual axonal processes exhibited both CB1 receptor and DbetaH immunoreactivities. Ultrastructural analysis confirmed that one-third of axon terminals containing CB1 immunolabeling also exhibited DbetaH labeling. Cortical neurons were also found to be targeted by separately labeled CB1- and DbetaH-containing axon terminals. In conclusion, the present neuroanatomical data suggest that cortical norepinephrine release may be modulated, in part, by CB1 receptors that are presynaptically distributed on noradrenergic axon terminals.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cannabinoid Receptor Modulators / metabolism*
  • Cannabis / adverse effects
  • Dopamine beta-Hydroxylase / metabolism
  • Immunohistochemistry
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / metabolism
  • Locus Coeruleus / physiopathology
  • Male
  • Marijuana Abuse / metabolism
  • Marijuana Abuse / physiopathology
  • Microscopy, Confocal
  • Microscopy, Immunoelectron
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Norepinephrine / metabolism*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / physiopathology
  • Presynaptic Terminals / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Synaptic Transmission / physiology*


  • Cannabinoid Receptor Modulators
  • Receptor, Cannabinoid, CB1
  • Dopamine beta-Hydroxylase
  • Norepinephrine