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.

  • Letter to the Editor
  • Published:

CREB1 haplotypes and the relative reinforcing value of nicotine

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 CREBαΔ−/− KO and MOR−/− KO mice do not exhibit nicotine-conditioned place preference.1, 4

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

Figure 1

References

  1. Walters CL, Cleck JN, Kuo YC, Blendy JA . Neuron 2005; 46: 933–943.

    Article  CAS  Google Scholar 

  2. Pluzarev O, Pandey SC . J Neurosci Res 2004; 77: 884–891.

    Article  CAS  Google Scholar 

  3. Lee PW, Lee YM . Mol Pharmacol 2003; 64: 1410–1418.

    Article  CAS  Google Scholar 

  4. Berrendero F, Kieffer BL, Maldonado R . J Neurosci 2002; 22: 10935–10940.

    Article  CAS  Google Scholar 

  5. Ray R, Jepson C, Patterson F, Strasser A, Rukstalis M, Perkins K et al. Psychopharmacology (Berl) 2006; 188: 355–363.

    Article  CAS  Google Scholar 

  6. Zhang Y, Wang D, Johnson AD, Papp AC, Sadee W . J Biol Chem 2005; 280: 32618–32624.

    Article  CAS  Google Scholar 

  7. The International Hapmap Project. http://www.hapmap.org.

  8. Carter KW MPAPLJ. http://genepicomau/projects/jlin. 2004.

  9. Lerman C, Wileyto EP, Patterson F, Rukstalis M, Audrian-McGovern J, Restine S et al. Pharmacogenomics J 2004; 4: 184–192.

    Article  CAS  Google Scholar 

  10. Sinwell JPS, Schaid DJ . Haplo Stats (Version 1.2.1) 2005.

Download references

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).

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Jepson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P Wileyto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F Patterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A A Strasser
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Rukstalis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K Perkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J Blendy
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C Lerman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C Lerman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4002002

This article is cited by

Search

Advanced search

Quick links