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Frequency-dependent modulation of dopamine release by nicotine

Nature Neuroscience volume 7, pages 581582 (2004) | Download Citation

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Abstract

Although nicotine activation of dopamine release is implicated in addiction, it also desensitizes nicotinic acetylcholine receptors (nAChRs), leading to a prolonged depression of evoked dopamine release. Here we show that nicotine's effects depend on the firing pattern of dopamine neurons, so that while desensitization of nAChRs indeed curbs dopamine released by stimuli emulating tonic firing, it allows a rapid rise in dopamine from stimuli emulating phasic firing patterns associated with incentive/salience paradigms. Nicotine may thus enhance the contrast of dopamine signals associated with behavioral cues.

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Acknowledgements

We thank Y. Schmitz and K. Larsen for critical reading of this manuscript, and E. Mosharov for software design. This work was supported by the National Institute on Drug Abuse, the Lowenstein Foundation and the Parkinson's Disease Foundation.

Author information

Affiliations

  1. Department of Neurology, Columbia University, 650 W 168th Street, New York, New York 10032, USA.

    • Hui Zhang
    •  & David Sulzer
  2. Department of Psychiatry, Columbia University and Department of Neuroscience, New York State Psychiatric Institute, New York, New York 10032, USA.

    • David Sulzer

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David Sulzer.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Frequency-dependent modulation of evoked dopamine release by nicotine with distal stimulation at the MFB. (a, b) Effect of number of stimulation pulses and frequency on the modulation of evoked dopamine release by nicotine (Nic, 300 nM). The effects of nicotine were nearly identical to that of local stimulation in the nAcc Shell (compare to Fig. 1 in the text). Experiments were performed in six horizontal slices from three pTH-GFP mice. The recording electrode was placed in the nAcc shell and the stimulating electrode was placed at the MFB outside of the striatum, at least 500 μm away from the recording site (mean ± s.e.m., n = 6; *P < 0.05 compared with respective control values by Student's test). Upper panels: Evoked dopamine release normalized to that elicited by 1p stimulation under control condition. Lower panels: Relative evoked DA release after nicotine and mecamylamine at different stimulation pulses.

  2. 2.

    Supplementary Methods

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DOI

https://doi.org/10.1038/nn1243

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