The Dopamine D3 Receptor Ser9Gly Polymorphism Modulates Prepulse Inhibition of the Acoustic Startle Reflex

Background The dopamine D3 receptor (DRD3) is suspected to modulate prepulse inhibition (PPI) in animals and humans, but definite conclusions cannot be drawn due to lack of selective DRD3 ligands. The Ser9Gly polymorphism is a common variant of the DRD3 gene and determines the gain of function of the D3 receptor. This is the first study to examine the influence of the DRD3 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 DRD3 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 D3 receptor and its levels depend on the Ser9Gly polymorphism.