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.

Bimodal control of stimulated food intake by the endocannabinoid system

Abstract

Activation of cannabinoid type-1 receptors (CB1) is universally recognized as a powerful endogenous orexigenic signal, but the detailed underlying neuronal mechanisms are not fully understood. Using combined genetic and pharmacological approaches in mice, we found that ventral striatal CB1 receptors exerted a hypophagic action through inhibition of GABAergic transmission. Conversely, brain CB1 receptors modulating excitatory transmission mediated the well-known orexigenic effects of cannabinoids.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Deletion of CB1 from cortical glutamatergic or GABAergic neurons has opposing effects on fasting-induced food intake.
Figure 2: The hyperphagic and hypophagic effects of THC depend on CB1-mediated modulation of glutamatergic and ventrostriatal GABAergic transmission, respectively.

References

  1. Matias, I. & Di Marzo, V. Trends Endocrinol. Metab. 18, 27–37 (2007).

    CAS  Article  Google Scholar 

  2. Piomelli, D. Nat. Rev. Neurosci. 4, 873–884 (2003).

    CAS  Article  Google Scholar 

  3. Kano, M., Ohno-Shosaku, T., Hashimotodani, Y., Uchigashima, M. & Watanabe, M. Physiol. Rev. 89, 309–380 (2009).

    CAS  Article  Google Scholar 

  4. Pagotto, U., Marsicano, G., Cota, D., Lutz, B. & Pasquali, R. Endocr. Rev. 27, 73–100 (2006).

    CAS  Article  Google Scholar 

  5. Marsicano, G. & Kuner, R. in Cannabinoids and the Brain (ed. Kofalvi, A.) 161–201 (Springer, New York, 2008).

  6. Kelley, A.E., Baldo, B.A., Pratt, W.E. & Will, M.J. Physiol. Behav. 86, 773–795 (2005).

    CAS  Article  Google Scholar 

  7. Shin, A.C., Zheng, H. & Berthoud, H.R. Physiol. Behav. 97, 572–580 (2009).

    CAS  Article  Google Scholar 

  8. Meena, H., Nakhate, K.T., Kokare, D.M. & Subhedar, N.K. Life Sci. 84, 156–163 (2009).

    CAS  Article  Google Scholar 

  9. Wiley, J.L. et al. Br. J. Pharmacol. 145, 293–300 (2005).

    CAS  Article  Google Scholar 

  10. Marsicano, G. et al. Nature 418, 530–534 (2002).

    CAS  Article  Google Scholar 

  11. Monory, K. et al. Neuron 51, 455–466 (2006).

    CAS  Article  Google Scholar 

  12. Monory, K. et al. PLoS Biol. 5, e269 (2007).

    Article  Google Scholar 

  13. Goebbels, S. et al. Genesis 44, 611–621 (2006).

    CAS  Article  Google Scholar 

  14. Yee, C.L., Wang, Y., Anderson, S., Ekker, M. & Rubenstein, J.L. J. Comp. Neurol. 517, 37–50 (2009).

    CAS  Article  Google Scholar 

  15. Hudson, B.D., Hebert, T.E. & Kelly, M.E. Mol. Pharmacol. 77, 1–9 (2010).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank F. George, P. Ciofi, V. Deroche-Gamonet and O. Moustie for help, D. Gonzales and the Genotyping Platform of the NeuroCentre Magendie for mouse genotyping, S.K. Nave, J. Rubenstein, M. Ekker, G. Schütz, T. Lemberger for providing Cre-expressing mice, and C.T. Wotjak, U. Pagotto, K. Monory, J. Lourenço, M. Vallée, B. Lutz and all the members of the Marsicano laboratory for valuable suggestions. This work was supported by AVENIR/INSERM and Fondation Bettencourt-Schueller (G.M.), Agence National de la Recherche (ANR-06-NEURO-043-01 to G.M.), the European Foundation for the Study of Diabetes (G.M.), European Union Seventh Framework Program (REPROBESITY, HEALTH-F2-2008-223713 to G.M.), European Commission Network of European Neuroscience Institutes (ENINET) (LSHM-CT-2005-19063 to G.M.), the Basque Country Government (GIC07/70-IT-432-07 to P.G.), Red de Trastornos Adictivos, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Gobierno de España (RD07/0001/2001 to P.G.) and Basque Country University (N.P.).

Author information

Authors and Affiliations

Authors

Contributions

L.B. designed and performed experiments. P.L. carried out part of the food-intake experiments. A.C., N.P. and P.G. performed the anatomical experiments. D.C., F.C. and P.V.P. contributed to experimental design. P.V.P. and G.M. wrote the manuscript. All the authors edited the manuscript. G.M. conceived and supervised the project.

Corresponding author

Correspondence to Giovanni Marsicano.

Ethics declarations

Competing interests

The authors have filed a patent application (European Patent Office, “Compositions targeting CB1 receptor for controlling food intake”, EP09306163.8) that is based, in part, on the results of this study.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–14 and Supplementary Methods (PDF 2038 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bellocchio, L., Lafenêtre, P., Cannich, A. et al. Bimodal control of stimulated food intake by the endocannabinoid system. Nat Neurosci 13, 281–283 (2010). https://doi.org/10.1038/nn.2494

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.2494

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing