The dopamine D3 receptor Ser9Gly polymorphism modulates prepulse inhibition of the acoustic startle reflex

Background: The dopamine D(3) receptor (DRD(3)) is suspected to modulate prepulse inhibition (PPI) in animals and humans, but definite conclusions cannot be drawn due to lack of selective DRD(3) ligands. The Ser9Gly polymorphism is a common variant of the DRD(3) gene and determines the gain of function of the D(3) receptor. This is the first study to examine the influence of the DRD(3) Ser9Gly polymorphism on human PPI. Methods: Prepulse inhibition was measured in 101 healthy male subjects presented with 75-dB and 85-dB prepulses at 30-, 60-, and 120-msec prepulse-pulse intervals. Subjects were grouped according to their DRD(3) status into a Gly/Gly, a Ser/Gly, and a Ser/Ser group. Results: Analyses of variance showed that at all prepulse and interval conditions, Gly/Gly individuals had the lowest PPI and the greatest onset latency facilitation and Ser/Ser individuals had the highest PPI and the lowest onset latency facilitation, while Ser/Gly individuals were intermediate. Conclusions: These results suggest that PPI is modulated by the D(3) receptor and its levels depend on the Ser9Gly polymorphism.