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Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice

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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Figure 1: Locomotor response to cocaine in mGluR5 WT (n = 14) and null mutant (n = 16) mice.
Figure 2: Food and cocaine reinforcement.
Figure 3: Extracellular NAcc DA levels in mGluR5 WT and null mutant mice.

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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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Correspondence to François 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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