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The effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism

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Abstract

Rationale

Prepulse inhibition (PPI) of the acoustic startle response, a measure of sensorimotor gating, can be enhanced by nicotine. Moreover, the TT genotype of the nicotinic acetylcholine receptor (nAChR) α3-subunit (CHRNA3) rs1051730 polymorphism has previously been associated with diminished PPI and nicotine dependence.

Objectives

We tested whether this CHRNA3 polymorphism also modulates the nicotine-induced enhancement of PPI.

Methods

We assessed the effect of nicotine on PPI, startle reactivity, and habituation in 52 healthy nonsmoking volunteers genotyped for CHRNA3 rs1051730 in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Additionally, cotinine plasma levels were measured.

Results

Nicotine significantly enhanced PPI in TT homozygotes only and tended to worsen PPI in TC and CC carriers. Additionally, nicotine significantly reduced startle habituation.

Conclusions

The present findings imply that the effect of nicotine on sensorimotor gating is modulated by nAChR α3-subunits. Thus, genetic variation in nicotinic receptor genes might be an important connecting link between early attentional processes and smoking behavior.

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Acknowledgments

This study was conducted within the framework of the Priority Program SPP1226 of the German Research Foundation (DFG, Deutsche Forschungsgemeinschaft): “Nicotine: Molecular and Physiological Effects in CNS” (http://ww.nicotine-research.com). This work was also supported by the 7th framework program of the European Union (ADAMS project, HEALTH-F4-2009-242257). Nadine Petrovsky and Michael Wagner are supported by the German Research Foundation (DFG Wa 731/7-1). Ulrich Ettinger is supported by the DFG Emmy Noether Programme (Et 31/2-1). Boris B. Quednow received a professorship grant from the Swiss National Science Foundation (SNSF, Grant No. PP00P1_123516). We thank Philipp A. Csomor for providing the emgBLINK software.

Conflict of interest

All authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany

    Nadine Petrovsky, Henrik Kessler, Rainald Mössner, Steffen Wolfsgruber, Wolfgang Maier & Michael Wagner

  2. Department of Psychology, University of Bonn, Kaiser-Karl-Ring 9, 53111, Bonn, Germany

    Nadine Petrovsky & Ulrich Ettinger

  3. Department of Psychiatry, Johannes Gutenberg-University of Mainz, Mainz, Germany

    Norbert Dahmen

  4. Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy, and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich, Switzerland

    Boris B. Quednow

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  1. Nadine Petrovsky
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  2. Ulrich Ettinger
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  4. Rainald Mössner
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  7. Wolfgang Maier
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  8. Michael Wagner
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  9. Boris B. Quednow
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Correspondence to Nadine Petrovsky.

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Petrovsky, N., Ettinger, U., Kessler, H. et al. The effect of nicotine on sensorimotor gating is modulated by a CHRNA3 polymorphism. Psychopharmacology 229, 31–40 (2013). https://doi.org/10.1007/s00213-013-3081-1

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  • DOI: https://doi.org/10.1007/s00213-013-3081-1

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