Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Part I: The Endocannabinoid System, Mechanisms of Action and Functions

Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic strength

International Journal of Obesity volume 30, pages S19–S23 (2006)Cite this article

Abstract

The CB1 cannabinoid receptor has attracted much recent interest because of the observation that CB1 receptor antagonists have efficacy in treating metabolic syndrome and obesity. CB1 receptors also mediate most of the psychotropic effects of Δ9-tetrahydrocannabinol (Δ9THC), the principal psychoactive component of cannabis. In addition, they are one component of an interesting and widespread paracrine signaling system, the endocannabinoid system. The endocannabinoid system is comprised of cannabinoid receptors, endogenous cannabinoids, and the metabolic pathways responsible for their synthesis and degradation. The details of the endocannabinoid system have been most thoroughly studied in the brain. Here it has been shown to be intimately involved in several forms of neuronal plasticity. That is, activation of CB1 receptors by endocannabinoids produces either short- or long-term changes in the efficacy of synaptic transmission. The behavioral consequences of these changes are many, but some of the most striking and relevant to the current symposium are those associated with endogenous reward and consumptive behavior.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA et al. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 2002; 54: 161–202.

    Article  CAS  Google Scholar 

  2. Jarai Z, Wagner JA, Varga K, Lake KD, Compton DR, Martin BR et al. Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Proc Natl Acad Sci USA 1999; 96: 14136–14141.

    Article  CAS  Google Scholar 

  3. Breivogel CS, Griffin G, Di Marzo V, Martin BR . Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol Pharmacol 2001; 60: 155–163.

    Article  CAS  Google Scholar 

  4. Hajos N, Freund TF . Distinct cannabinoid sensitive receptors regulate hippocampal excitation and inhibition. Chem Phys Lipids 2002; 121: 73–82.

    Article  CAS  Google Scholar 

  5. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI . Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990; 346: 561–564.

    Article  CAS  Google Scholar 

  6. Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC . Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 1991; 11: 563–583.

    Article  CAS  Google Scholar 

  7. Katona I, Sperlagh B, Sik A, Kafalvi A, Vizi ES, Mackie K et al. Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons. J Neurosci 1999; 19: 4544–4558.

    Article  CAS  Google Scholar 

  8. Marsicano G, Lutz B . Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain. Eur J Neurosci 1999; 11: 4213–4225.

    Article  CAS  Google Scholar 

  9. Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A et al. CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 2003; 302: 84–88.

    Article  CAS  Google Scholar 

  10. Hoffman AF, Lupica CR . Mechanisms of cannabinoid inhibition of GABA(A) synaptic transmission in the hippocampus. J Neurosci 2000; 20: 2470–2479.

    Article  CAS  Google Scholar 

  11. Hajos N, Katona I, Naiem SS, MacKie K, Ledent C, Mody I et al. Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations. Eur J Neurosci 2000; 12: 3239–3249.

    Article  CAS  Google Scholar 

  12. Freund TF, Katona I, Piomelli D . Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 2003; 83: 1017–1066.

    Article  CAS  Google Scholar 

  13. Walker JM, Krey JF, Chu CJ, Huang SM . Endocannabinoids and related fatty acid derivatives in pain modulation. Chem Phys Lipids 2002; 121: 159–172.

    Article  CAS  Google Scholar 

  14. Gulyas AI, Cravatt BF, Bracey MH, Dinh TP, Piomelli D, Boscia F et al. Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala. Eur J Neurosci 2004; 20: 441–458.

    Article  CAS  Google Scholar 

  15. Walker JM, Huang SM, Strangman NM, Tsou K, Sanudo-Pena MC . Pain modulation by release of the endogenous cannabinoid anandamide. Proc Natl Acad Sci USA 1999; 96: 12198–12203.

    Article  CAS  Google Scholar 

  16. Giuffrida A, Parsons LH, Kerr TM, Rodriguez de Fonseca F, Navarro M, Piomelli D . Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nat Neurosci 1999; 2: 358–363.

    Article  CAS  Google Scholar 

  17. Luk T, Jin W, Zvonok A, Lu D, Lin XZ, Chavkin C et al. Identification of a potent and highly efficacious, yet slowly desensitizing CB1 cannabinoid receptor agonist. Br J Pharmacol 2004; 142: 495–500.

    Article  CAS  Google Scholar 

  18. Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET et al. Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry 2001; 58: 322–328.

    Article  CAS  Google Scholar 

  19. Wilson RI, Kunos G, Nicoll RA . Presynaptic specificity of endocannabinoid signaling in the hippocampus. Neuron 2001; 31: 453–462.

    Article  CAS  Google Scholar 

  20. Wilson RI, Nicoll RA . Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature 2001; 410: 588–592.

    Article  CAS  Google Scholar 

  21. Alger BE . Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids. Prog Neurobiol 2002; 68: 247–286.

    Article  CAS  Google Scholar 

  22. Jo YH, Chen YJ, Chua Jr SC, Talmage DA, Role LW . Integration of endocannabinoid and leptin signalling in an appetite-related neural circuit. Neuron 2005; 48: 1055–1066.

    Article  CAS  Google Scholar 

  23. Stella N . Cannabinoid signaling in glial cells. Glia 2004; 48: 267–277.

    Article  Google Scholar 

  24. Bacci A, Huguenard JR, Prince DA . Long-lasting self-inhibition of neocortical interneurons mediated by endocannabinoids. Nature 2004; 431: 312–316.

    Article  CAS  Google Scholar 

  25. Kreitzer AC, Carter AG, Regehr WG . Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. Neuron 2002; 34: 787–796.

    Article  CAS  Google Scholar 

  26. Gerdeman GL, Lovinger DM . Emerging roles for endocannabinoids in long-term synaptic plasticity. Br J Pharmacol 2003; 140: 781–789.

    Article  CAS  Google Scholar 

  27. Lupica CR, Riegel AC, Hoffman AF . Marijuana and cannabinoid regulation of brain reward circuits. Br J Pharmacol 2004; 143: 227–234.

    Article  CAS  Google Scholar 

  28. Sjostrom PJ, Turrigiano GG, Nelson SB . Neocortical LTD via coincident activation of presynaptic NMDA and cannabinoid receptors. Neuron 2003; 39: 641–654.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anesthesiology, University of Washington School of Medicine, Seattle, WA, USA

    K Mackie

Authors
  1. K Mackie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K Mackie.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mackie, K. Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic strength. Int J Obes 30 (Suppl 1), S19–S23 (2006). https://doi.org/10.1038/sj.ijo.0803273

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0803273

Keywords

This article is cited by

Search

Advanced search

Quick links