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Role of β2-containing nicotinic acetylcholine receptors in auditory event-related potentials

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Abstract

Rationale

Nicotine improves sensory processing in schizophrenic individuals, as measured by changes in auditory event-related potentials (ERPs). Nicotine administration also alters ERPs in mice by increasing the amplitude and gating of the P20 ERP component while decreasing the amplitude of the N40 ERP component. Less is known about the role of specific nicotinic acetylcholine receptor (nAChR) subtypes.

Objectives

In this study, we examined whether nAChRs containing the β2 subunit contribute to nicotine’s effects on auditory ERPs.

Materials and methods

We tested the effect of nicotine in wild-type mice and mice lacking the β2 nAChR subunit. Mice underwent stereotaxic implantation of stainless steel electrodes located in the CA3 region of the hippocampus, and 50 paired click stimuli were delivered during each drug condition.

Results

There was no significant difference in P20 or N40 amplitude or gating between genotypes during the control condition, suggesting that β2-containing receptors are not essential for the baseline auditory ERP response. Nicotine increased P20 amplitude and enhanced gating in wild-type and β2 knockout mice, but only decreased N40 amplitude in wild-type mice. There was no effect of nicotine on N40 gating in either genotype.

Conclusions

β2-containing receptors are necessary for nicotine’s effects on the N40 component of the mouse auditory ERP. These results suggest that β2-containing nAChRs modulate sensory processing and may serve as a therapeutic target in schizophrenic individuals.

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Acknowledgements

We thank Prof. Caryn Lerman and Dr. Tobias Halene for critical readings of the manuscript. This work was supported by P50-CA-084718 (Caryn Lerman, PI) and P50 MH-064045 (Raquel E. Gur, PI) and AA15632, DA00436 (Marina R. Picciotto, PI).

Conflicts of interest

The authors have no conflicts of interest to report and agree to share data with the journal if requested. All experiments comply with the laws of the United States of America.

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Authors and Affiliations

  1. Stanley Center for Experimental Therapeutics, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, 19312, USA

    Noam D. Rudnick, Christine Koehler & Steven J. Siegel

  2. Department of Psychiatry, Yale University, New Haven, CT, 06511, USA

    Marina R. Picciotto

  3. Transdisciplinary Tobacco Use Research Center, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, 19312, USA

    Steven J. Siegel

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  1. Noam D. Rudnick
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  2. Christine Koehler
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  3. Marina R. Picciotto
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  4. Steven J. Siegel
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Correspondence to Steven J. Siegel.

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Rudnick, N.D., Koehler, C., Picciotto, M.R. et al. Role of β2-containing nicotinic acetylcholine receptors in auditory event-related potentials. Psychopharmacology 202, 745–751 (2009). https://doi.org/10.1007/s00213-008-1358-6

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  • DOI: https://doi.org/10.1007/s00213-008-1358-6

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