Rationale: Emerging evidence from agonist-antagonist studies suggests a role for the dopamine D(3) 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 D(3) 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 D(3) receptor in the mediation of human PPI, although a contribution from ropinirole's agonistic activity at the D(2) receptor cannot be entirely excluded. Firm conclusions on the role of the D(3) receptor in the modulation of human PPI can only be drawn with the use of genetic approaches or more selective ligands for this receptor.