1. ¹University Hospital of Psychiatry Zurich, Experimental Psychopathology and Brain Imaging, Zurich, Switzerland
2. ²Laboratory of Behavioural Neurobiology, ETH Zurich, Schwerzenbach, Switzerland
3. ³Department of Psychiatry, University of California at San Diego, La Jolla, CA, USA

Correspondence: Dr FX Vollenweider, University Hospital of Psychiatry Zurich, Lenggstrasse 31, CH-8029 Zurich, Switzerland. Tel: +41 44 3822604, Fax: +41 44 3843396, E-mail: vollen@bli.unizh.ch

Received 14 December 2006; Revised 12 March 2007; Accepted 13 March 2007; Published online 25 April 2007.

Abstract

Schizophrenia patients exhibit deficits in sensory gating as indexed by reduced prepulse inhibition (PPI) and P50 suppression, which have been linked to psychotic symptom formation and cognitive deficits. Although recent evidence suggests that atypical antipsychotics might be superior over typical antipsychotics in reversing PPI and P50 suppression deficits not only in schizophrenia patients, but also in healthy volunteers exhibiting low levels of PPI, the impact of typical antipsychotics on these gating measures is less clear. To explore the impact of the dopamine D₂-like receptor system on gating and cognition, the acute effects of haloperidol on PPI, P50 suppression, and cognition were assessed in 26 healthy male volunteers split into subgroups having low vs high PPI or P50 suppression levels using a placebo-controlled within-subject design. Haloperidol failed to increase PPI in subjects exhibiting low levels of PPI, but attenuated PPI in those subjects with high sensorimotor gating levels. Furthermore, haloperidol increased P50 suppression in subjects exhibiting low P50 gating and disrupted P50 suppression in individuals expressing high P50 gating levels. Independently of drug condition, high PPI levels were associated with superior strategy formation and execution times in a subset of cognitive tests. Moreover, haloperidol impaired spatial working memory performance and planning ability. These findings suggest that dopamine D₂-like receptors are critically involved in the modulation of P50 suppression in healthy volunteers, and to a lesser extent also in PPI among subjects expressing high sensorimotor gating levels. Furthermore, the results suggest a relation between sensorimotor gating and working memory performance.