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Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence


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.

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Figure 1: Adolescent nicotine exposure affects measures of attentional performance, mGluR2 levels and long-term function on the long term.
Figure 2: Short-term depression in mPFC is reduced 5 weeks after nicotine exposure during adolescence.
Figure 3: Intra-mPFC infusion of mGluR2/3 agonist LY379268 reverses long-term attentional disturbances in rats exposed to nicotine as adolescents.


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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).

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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.

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Correspondence to Sabine Spijker.

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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).

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