CREB1 haplotypes and the relative reinforcing value of nicotine (original) (raw)

Molecular Psychiatry volume 12, pages 615–617 (2007)Cite this article

Genetic and pharmacological studies in mice have demonstrated an important role of the _μ_-opioid receptor (MOR) and cAMP responsive element-binding protein (CREB) in nicotine reward/dependence. We tested for an interaction between these two genes (OPRM1 and CREB1) in a human pharmacogenetic laboratory study.

Preclinical studies support the importance of both CREB and MOR in nicotine reward.1 Nicotine increases phosphorylation of CREB (P-CREB) in the ventral tegmental area,1 while nicotine withdrawal decreases P-CREB.2 Nicotine-induced P-CREB increase is absent in MOR−/− knockout (KO) mice and is also blocked by the MOR antagonist naloxone in wild-type mice.1 The MOR promoter has a cAMP-responsive element that binds P-CREB, which is thought to drive expression of MOR.1, 3 Finally, the CREB_α_Δ−/− KO and MOR−/− KO mice do not exhibit nicotine-conditioned place preference.1, 4

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Acknowledgements

This research was supported by grants from the National Institute on Drug Abuse (RO1 DA017555-03) and National Cancer Institute (P50 CA/DA84718) (CL).

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Authors and Affiliations

  1. Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA
    R Ray & J Blendy
  2. Department of Psychiatry, Transdisciplinary Tobacco Use Research Center, University of Pennsylvania, Philadelphia, PA, USA
    R Ray, C Jepson, P Wileyto, F Patterson, A A Strasser, M Rukstalis, J Blendy & C Lerman
  3. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    K Perkins

Authors

  1. R Ray
  2. C Jepson
  3. P Wileyto
  4. F Patterson
  5. A A Strasser
  6. M Rukstalis
  7. K Perkins
  8. J Blendy
  9. C Lerman

Corresponding author

Correspondence toC Lerman.

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Ray, R., Jepson, C., Wileyto, P. et al. CREB1 haplotypes and the relative reinforcing value of nicotine.Mol Psychiatry 12, 615–617 (2007). https://doi.org/10.1038/sj.mp.4002002

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