Abstract
Tobacco smoking and nicotine exposure during adolescence interfere with prefrontal cortex (PFC) development and lead to cognitive impairments in later life. The molecular and cellular underpinnings of these consequences remain elusive. We found that adolescent nicotine exposure induced lasting attentional disturbances and reduced mGluR2 protein and function on presynaptic terminals of PFC glutamatergic synapses. Restoring mGluR2 activity in vivo by local infusion of a group II mGluR agonist in adult rats that received nicotine as adolescents rescued attentional disturbances.
Similar content being viewed by others
References
Casey, B.J., Tottenham, N., Liston, C. & Durston, S. Trends Cogn. Sci. 9, 104–110 (2005).
Chassin, L., Presson, C.C., Rose, J.S. & Sherman, S.J. Health Psychol. 15, 478–484 (1996).
Slotkin, T.A. Toxicol. Appl. Pharmacol. 198, 132–151 (2004).
Jacobsen, L.K. et al. Biol. Psychiatry 57, 56–66 (2005).
Jacobsen, L.K., Slotkin, T.A., Mencl, W.E., Frost, S.J. & Pugh, K.R. Neuropsychopharmacology 32, 2453–2464 (2007).
Mathers, M., Toumbourou, J.W., Catalano, R.F., Williams, J. & Patton, G.C. Addiction 101, 948–958 (2006).
WHO-Europe. Health policy for children and adolescents. (No. 4) (eds. C. Currie, et al.) (Copenhagen, 2004).
Spear, L.P. Neurosci. Biobehav. Rev. 24, 417–463 (2000).
Counotte, D.S. et al. Neuropsychopharmacology 34, 299–306 (2009).
Pattij, T. & Vanderschuren, L.J. Trends Pharmacol. Sci. 29, 192–199 (2008).
Robbins, T.W. Psychopharmacology (Berl.) 163, 362–380 (2002).
Dalley, J.W., Cardinal, R.N. & Robbins, T.W. Neurosci. Biobehav. Rev. 28, 771–784 (2004).
Mateo, Z. & Porter, J.T. Neuroscience 146, 1062–1072 (2007).
Chudasama, Y. et al. Behav. Brain Res. 146, 105–119 (2003).
Zucker, R.S. Annu. Rev. Neurosci. 12, 13–31 (1989).
Acknowledgements
We thank Y. van Mourik, M. Stegeman, H. Lodder, B. Lodder, C. de Kock and R. Binnekade for excellent technical assistance. Funding was received from Netherlands Organization for Scientific Research (D.S.C., N.A.G., S.S., H.D.M., T.P., A.N.M.S. and A.B.S.), Center for Medical Systems Biology (K.W.L. and R.C.v.d.S.) and VU University (H.D.M.; Starting Independent Research Grant, VU European Research Council).
Author information
Authors and Affiliations
Contributions
D.S.C. and N.A.G. contributed equally to the experiments in this paper. D.S.C., K.W.L., A.B.S. and S.S. designed the molecular experiments. N.A.G. and H.D.M. designed the physiological experiments. D.S.C., A.N.M.S., S.S. and T.P. designed the behavioral experiments. D.S.C. and R.C.v.d.S. executed the molecular experiments. N.A.G. executed physiological experiments. D.S.C. and D.S. executed behavioral experiments. D.S.C., M.L. and S.S. analyzed molecular experiments. N.A.G. and H.D.M. analyzed physiological experiments. D.S.C. and T.P. analyzed behavioral experiments. D.S.C., H.D.M., T.P. and S.S. wrote the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–10, Supplementary Tables 1–4, Supplementary Methods, Supplementary Results and Supplementary Discussion (PDF 2357 kb)
Rights and permissions
About this article
Cite this article
Counotte, D., Goriounova, N., Li, K. et al. Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence. Nat Neurosci 14, 417–419 (2011). https://doi.org/10.1038/nn.2770
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn.2770
- Springer Nature America, Inc.