Characterization of cannabinoid-1 receptors in the locus coeruleus: relationship with mu-opioid receptors

Brain Res. 2010 Feb 2;1312:18-31. doi: 10.1016/j.brainres.2009.11.023. Epub 2009 Nov 18.


The locus coeruleus (LC)-norepinephrine system is a target of both cannabinoid and opioid actions. The present study investigated the anatomical distribution of cannabinoid-1 receptor (CB1r) in the LC and its association with mu-opioid receptor (MOR). Immunoreactivity for CB1r was localized to pre- and postsynaptic cellular profiles in the LC, 82% of which were dual-labeled for tyrosine hydroxylase (TH). Of the CB1r-immunoreactive structures, 66% were somatodendritic profiles, 22% were axon terminals, and the remaining 12% were associated with glial and small unmyelinated axon-like structures. CB1r immunoreactivity (-ir) in somatodendritic profiles was more often localized to the cytoplasm, whereas CB1r-ir located in axon terminals was more commonly localized on the plasma membrane. Somatodendritic profiles with CB1r-ir typically received input from axon terminals forming asymmetric-type synapses. In contrast, presynaptic profiles with CB1r-ir typically formed symmetric synaptic specializations. Anatomical studies confirmed the co-existence of MOR and CB1r-ir in common somatodendritic compartments of catecholaminergic neurons in the LC, and also revealed CB1r-positive axon terminals forming synaptic contact with MOR-containing dendrites. Our results provide evidence for a heterogeneous distribution of CB1r in the LC and demonstrate that CB1r and MOR co-exist in cellular profiles in this region. These data suggest important potential interactions between cannabinoid and opioid systems in LC neuronal profiles that may impact noradrenergic tone.

MeSH terms

  • Animals
  • Locus Coeruleus / cytology
  • Locus Coeruleus / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Microscopy, Immunoelectron / methods
  • Neurons / cytology
  • Neurons / metabolism
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / deficiency
  • Receptor, Cannabinoid, CB1 / physiology*
  • Receptor, Cannabinoid, CB1 / ultrastructure
  • Receptors, Opioid, mu / metabolism*
  • Tyrosine 3-Monooxygenase / metabolism


  • Receptor, Cannabinoid, CB1
  • Receptors, Opioid, mu
  • Tyrosine 3-Monooxygenase