Disruption of prepulse inhibition of the startle reflex by the preferential D(3) agonist ropinirole in healthy males.

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.