The International Journal of Neuropsychopharmacology

Research Article

Sensorimotor gating and D2 receptor signalling: evidence from a molecular genetic approach

Christoph Völtera1a2, Michael Riedela2a3, Nicola Wöstmanna2, Désirée S. Aicherta2, Sarah Loboa4, Anna Costaa2, Anne Schmechtiga5, David A. Colliera6, Annette M. Hartmanna2, Ina Gieglinga2, Hans-Jürgen Möllera2, Boris B. Quednowa7, Dan Rujescua2, Veena Kumaria4a8* and Ulrich Ettingera1a2 c1*

a1 Department of Psychology, University of Munich, Germany

a2 Department of Psychiatry, University of Munich, Germany

a3 Klinik für Psychiatrie, Psychotherapie, Gerontopsychiatrie und Neurologie, Rottweil, Germany

a4 Department of Psychology, Institute of Psychiatry, King's College London, UK

a5 Department of Neuroimaging, Institute of Psychiatry, King's College London, UK

a6 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK

a7 University Hospital of Psychiatry, Clinical and Experimental Pharmacopsychology, University of Zurich, Switzerland

a8 NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust, London, UK

Abstract

Converging evidence from pharmacological investigations, genetic association studies and schizophrenia research indicates an important influence of the dopamine system on sensorimotor gating as measured by prepulse inhibition (PPI) of the acoustic startle response. In particular, D2 receptor agonists have been shown to disrupt PPI in humans and rodents. In the present study, we investigated the associations of two functional DRD2 related single nucleotide polymorphisms (rs4648317 and rs1800497, the latter also known as DRD2/ANKK1 Taq1A) with PPI in two independent healthy human samples (overall n=197; Munich n=101; London n=96). Taq1A is a prominent marker of striatal D2 receptor signalling and was therefore hypothesized to impact on PPI. In line with our hypothesis, we report here reduced PPI levels in individuals with higher striatal D2 receptor signalling as indicated by the Taq1A genotype. Meta-analysis across both samples confirmed this finding. In contrast, an association between rs4648317 and PPI found in the Munich sample could not be confirmed in the London sample. Overall, the present study helps to bridge the gap between pharmacological manipulations of PPI and molecular genetics of the dopaminergic system.

(Received May 02 2011)

(Reviewed July 26 2011)

(Revised November 15 2011)

(Accepted November 16 2011)

(Online publication January 16 2012)

Correspondence:

c1 Address for correspondence: Dr U. Ettinger, Department of Psychiatry, University of Munich, Nussbaumstr. 7, 80336 Munich, Germany. Tel: +49 89 5160 3499 Fax: +49 89 5160 5789 Email: ulrich.ettinger@med.uni-muenchen.de

Footnotes

* These authors served as Joint Senior authors.

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