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Addiction

Identity of reward

Nature Reviews Neuroscience volume 5, page 901 (2004)Cite this article

Nicotine dependence begins with the binding of nicotine to nicotinic acetylcholine receptors (nAChRs) — pentameric cation-permeable ligand-gated ion channels that are normally activated by the endogenous neurotransmitter acetylcholine. At present, 12 nAChRs subunits have been identified, and many combinations can give rise to functional receptors. In this study, the authors generated 'knock-in' mice, in which the wild-type α4 subunit is replaced with one that contains a point mutation, leucine to alanine, within the putative pore-forming M2 domain and, as a result, is hypersensitive to nicotine.

They found that nicotine could induce calcium influx in cultured ventral midbrain neurons from mutant mice at a concentration that was 40-fold lower than for the wild-type cultures. Chronic administration of low doses of nicotine (50-fold lower than that found in the blood of smokers) resulted in a robust functional upregulation — an increase in the neuron's responsiveness to acetylcholine — in cultures from mutant but not wild-type mice. In addition, low concentrations of nicotine resulted in increased action potential firing frequency in the dopaminergic neurons from mutant mice, but had little effect on those from wild-type animals.

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References

ORIGINAL RESEARCH PAPER

  1. Tapper, A. R. et al. Nicotine activation of α4* receptors: sufficient for reward, tolerance, and sensitization. Science 306, 1029–1032 (2004)

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FURTHER READING

  1. Laviolette, S. R. & van der Kooy, D. The neurobiology of nicotine addiction: bridging the gap from molecules to behaviour. Nature Rev. Neurosci. 5, 55–65 (2004)

    Article  CAS  Google Scholar 

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Authors
  1. Jane Qiu
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Qiu, J. Identity of reward. Nat Rev Neurosci 5, 901 (2004). https://doi.org/10.1038/nrn1565

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  • DOI: https://doi.org/10.1038/nrn1565

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