Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice (original) (raw)

Nature Neuroscience volume 4, pages 873–874 (2001)Cite this article

Abstract

Both ionotropic and metabotropic glutamate receptors (mGluRs) are involved in the behavioral effects of pyschostimulants1,2,3; however, the specific contributions of individual mGluR subtypes remain unknown. Here we show that mice lacking the mGluR5 gene do not self-administer cocaine, and show no increased locomotor activity following cocaine treatment, despite showing cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA) levels similar to wild-type (WT) mice. These results demonstrate a significant contribution of mGlu5 receptors to the behavioral effects of cocaine, and suggest that they may be involved in cocaine addiction.

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References

  1. Kim, J. H. & Vezina, P. J. Pharmacol. Exp. Ther. 284, 317–322 (1998).
    CAS PubMed Google Scholar
  2. Vezina, P. & Kim, J. H. Neurosci. Behav. Rev. 23, 577–589 (1999).
    Article CAS Google Scholar
  3. Swanson, C. J. & Kalivas, P. W. J. Pharmacol. Exp. Ther. 292, 406–414 (2000).
    CAS PubMed Google Scholar
  4. Smith, J. A. et al. Brain Res. 683, 264–269 (1995).
    Article CAS Google Scholar
  5. Pierce, R. C., Bell, K., Duffy, P. & Kalivas, P. W. J. Neurosci. 16, 1550–1560 (1996).
    Article CAS Google Scholar
  6. Koob, G. F., Sanna, P. P. & Bloom, F. E. Neuron 21, 467–476 (1998).
    Article CAS Google Scholar
  7. White, F. J. & Kalivas, P. W. Drug Alcohol Depend. 51, 141–153 (1998).
    Article CAS Google Scholar
  8. Tallaksen-Greene, S. J., Kaatz, K. W., Romano, C. & Albin, R. L. Brain Res. 780, 210–217 (1998).
    Article CAS Google Scholar
  9. Ghasemzadeh, M. B., Nelson, L. C., Lu, X. Y. & Kalivas, P. W. J. Neurochem. 72, 157–165 (1999).
    Article CAS Google Scholar
  10. Caine, S. B., Negus, S. S. & Mello, N. K. Psychopharmacology 147, 22–24 (1999).
    Article CAS Google Scholar
  11. Gasparini, F. et al. Neuropharmacology 38, 1493–1503 (1999).
    Article CAS Google Scholar
  12. Zocchi, A. et al. Neuroscience 82, 521–528 (1998).
    Article CAS Google Scholar
  13. Miner, L. L. et al. Neuroreport 6, 2314–2316 (1995).
    Article CAS Google Scholar
  14. Parson, L. H. & Justice, J. B. J. Neurochem. 61, 1611–1619 (1993).
    Article Google Scholar

Download references

Acknowledgements

We thank A. Morrison and C. Corti for their contribution in the establishment and detection of the mutation, F. Fornai and E. Grouzman for HPLC analyses, and M. Geyer, D. Lavery and E. Ratti for reviewing the manuscript. This work was supported by GlaxoSmithKline R&D.

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Author notes

  1. Christian Chiamulera and Mark P. Epping-Jordan: The first two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biology, GlaxoSmithKline Laboratories, via Fleming 4, Verona, 37100, Italy
    Christian Chiamulera, Alessandro Zocchi, Clara Marcon, Stefano Tacconi & Mauro Corsi
  2. GlaxoSmithKline R&D, Institut de Biologie Cellulaire et de Morphologie, rue du Bugnon 9, 1005 Lausanne, Switzerland
    Mark P. Epping-Jordan, Cécilia Cottiny & François Conquet
  3. Neuromed Institute, via Atinense 18, Pozzilli, 86077, Italy
    Alessandro Zocchi & Francesco Orzi
  4. Department of Neurological Sciences, University of Rome La Sapienza, Piazzale Aldo Moro 5, Rome, 00185, Italy
    Francesco Orzi

Authors

  1. Christian Chiamulera
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  2. Mark P. Epping-Jordan
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  3. Alessandro Zocchi
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  4. Clara Marcon
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  5. Cécilia Cottiny
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  6. Stefano Tacconi
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  7. Mauro Corsi
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  8. Francesco Orzi
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  9. François Conquet
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Corresponding author

Correspondence toFrançois Conquet.

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Chiamulera, C., Epping-Jordan, M., Zocchi, A. et al. Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice.Nat Neurosci 4, 873–874 (2001). https://doi.org/10.1038/nn0901-873

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