Disruption of prepulse inhibition of the startle reflex by the preferential D₃ agonist ropinirole in healthy males

Rationale: Emerging evidence from agonist-antagonist studies suggests a role for the dopamine D₃ receptor subtype in the regulation of PPI in animals, but such evidence is lacking for human subjects. Objectives: This study examines the effect of the preferential D₃ agonist ropinirole on PPI in humans. Methods: PPI was tested in 12 healthy men in three sessions associated with ropinirole 0.25 mg, ropinirole 0.5 mg, or placebo according to a balanced, crossover, double-blind design. Two prepulses (75- and 85-dB white noise bursts) and two lead intervals (50 and 80 ms) were employed. Results: Ropinirole 0.5 mg significantly reduced prepulse inhibition (PPI) with both prepulses at the 80-ms lead intervals. There was no effect of treatment on startle amplitude and habituation. Conclusions: These results suggest a role for the dopamine D₃ receptor in the mediation of human PPI, although a contribution from ropinirole's agonistic activity at the D₂ receptor cannot be entirely excluded. Firm conclusions on the role of the D₃ receptor in the modulation of human PPI can only be drawn with the use of genetic approaches or more selective ligands for this receptor.