Sensorimotor gating and D-2 receptor signalling: evidence from a molecular genetic approach

Christoph Voelter, Michael Riedel, Nicola Woestmann, Desiree S. Aichert, Sarah Lobo, Anna Costa, Anne Schmechtig, David A. Collier, Annette M. Hartmann, Ina Giegling, Hans-Juergen Moeller, Boris B. Quednow, Dan Rujescu, Veena Kumari, Ulrich Ettinger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

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, D-2 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.

Original languageEnglish
Pages (from-to)1427-1440
Number of pages14
JournalInternational journal of neuropsychopharmacology
Volume15
Issue number10
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Acoustic startle response
  • dopamine
  • DRD2
  • prepulse inhibition
  • Taq1a
  • ACOUSTIC STARTLE RESPONSE
  • SCHIZOTYPAL PERSONALITY-DISORDER
  • PREPULSE INHIBITION
  • SCHIZOPHRENIC-PATIENTS
  • ANIMAL-MODEL
  • BINDING CHARACTERISTICS
  • NICOTINE DEPENDENCE
  • HEALTHY-VOLUNTEERS
  • DOPAMINE RELEASE
  • A1 ALLELE

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