Clozapine enhances prepulse inhibition in healthy humans with low but not with high prepulse inhibition levels.
BACKGROUND
Atypical antipsychotics have been assessed for normalization effects on deficient sensory gating as indexed by prepulse inhibition (PPI) in schizophrenics with generally positive, although somewhat conflicting, results.


METHODS
We tested the acute effect of clozapine on startle, PPI, and attention, working memory, and executive functioning in 28 healthy male volunteers with low versus high PPI levels using a placebo-controlled within-subject design.


RESULTS
Clozapine significantly increased PPI levels obtained at short lead intervals of 60 and 120 msec in subjects with low PPI performance but showed no effect in subjects with high PPI. Clozapine also caused a mild cognitive impairment on attention and pattern recognition memory tests. No correlations between cognitive measures and PPI performance were found. Moreover, low and high PPI performers were shown to exhibit stable levels of PPI across three separate nondrug testing days.


CONCLUSIONS
Clozapine increases sensorimotor gating in healthy subjects with low but not high PPI levels in a manner comparable to that seen in clozapine-treated schizophrenia patients. Healthy subjects with low PPI level in combination with genetic studies may provide a translational model to elucidate the neuronal basis of PPI deficits and to test the efficacy of novel antipsychotic medication.
Vollenweider
Franz X
FX
University Hospital of Psychiatry, Clinical Research, Zürich, Switzerland. vollen@bli.unizh.ch
Barro
Martine
M
Csomor
Philipp A
PA
Feldon
Jorame
J
D000161:Acoustic Stimulation; D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001288:Attention / Q000187:drug effects; D003024:Clozapine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D009483:Neuropsychological Tests; D010555:Personality Inventory / Q000706:statistics & numerical data; D013216:Reflex, Startle / Q000187:drug effects*
D014150:Antipsychotic Agents; D003024:Clozapine