Identification of the cannabinoid receptor type 1 in serotonergic cells of raphe nuclei in mice

Neuroscience. 2007 May 25;146(3):1212-9. doi: 10.1016/j.neuroscience.2007.02.021. Epub 2007 Mar 23.


The endocannabinoid system (ECS) possesses neuromodulatory functions by influencing the release of various neurotransmitters, including GABA, noradrenaline, dopamine, glutamate and acetylcholine. Even though there are studies indicating similar interactions between the ECS and the serotonergic system, there are no results showing clear evidence for type 1 cannabinoid receptor (CB1) location on serotonergic neurons. In this study, we show by in situ hybridization that a low but significant fraction of serotonergic neurons in the raphe nuclei of mice contains CB1 mRNA as illustrated by the coexpression with the serotonergic marker gene tryptophane hydroxylase 2, the rate limiting enzyme for the serotonin synthesis. Furthermore, by double immunohistochemistry and confocal microscopy, we were able to detect CB1 protein on serotonergic fibers and synapses expressing the serotonin uptake transporter in the hippocampus and the amygdala. Our findings indicate that the CB1-mediated regulation of serotonin release can depend in part on a direct cross-talk between the two systems at single cell level, which might lead to functional implications in the modulation of emotional states.

MeSH terms

  • Amygdala / cytology
  • Amygdala / metabolism
  • Animals
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism
  • Female
  • Genetic Markers
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Isoenzymes / genetics
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Nerve Fibers / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Raphe Nuclei / cytology*
  • Raphe Nuclei / metabolism*
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Serotonin / physiology*
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Synapses / metabolism
  • Tryptophan Hydroxylase / genetics


  • Genetic Markers
  • Isoenzymes
  • RNA, Messenger
  • Receptor, Cannabinoid, CB1
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, mouse
  • Serotonin
  • Tph2 protein, mouse
  • Tryptophan Hydroxylase