The effects of dopamine agonists on prepulse inhibition in healthy men depend on baseline PPI values

Rationale and objectives: Dopamine (DA) agonists reliably disrupt prepulse inhibition (PPI) of the startle reflex in animals but less so in humans despite cross-species similarities in the neural regulation of PPI. This study examines whether individual variation in baseline PPI may account for the inconsistencies in DA agonist-induced PPI disruption in humans. Methods: Baseline PPI measures were obtained from 32 healthy adult men. Subjects were subsequently tested in three sessions after ingestion of placebo or active drug in a balanced double-blind design. Seventeen subjects were given 0.05 and 0.1 mg of pergolide (a direct DA agonist) and 15 subjects were given 100 and 200 mg of amantadine (an indirect DA agonist). In each treatment group, subjects were assigned to "high" and "low" PPI subgroups based on the median split of their baseline PPI. Results: Amantadine and pergolide disrupted PPI in high- but not in low-PPI subjects. In contrast, low-PPI subjects showed a trend towards PPI facilitation especially with pergolide. Conclusions: Our results suggest that baseline PPI is an important determinant of the effect of DA agonists on PPI.