The effects of dopamine agonists on prepulse inhibition in healthy men depend on baseline PPI values.
OBJECTIVE
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.
Bitsios
Panos
P
Department of Psychiatry and Behavioural Sciences, Faculty of Medicine, University of Crete, P.O. BOX 2208, Heraklion, 71003, Crete, Greece. pbitsios@med.uoc.gr
Giakoumaki
Stella G
SG
Frangou
Sophia
S
D000161:Acoustic Stimulation; D000328:Adult; D000547:Amantadine / Q000494:pharmacology*; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000494:pharmacology*; D004311:Double-Blind Method; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006801:Humans; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D010479:Pergolide / Q000494:pharmacology*; D013216:Reflex, Startle / Q000187:drug effects*; D013337:Students, Medical
D018491:Dopamine Agonists; D010479:Pergolide; D000547:Amantadine