Effects of procyclidine on prepulse inhibition of the acoustic startle response in healthy human volunteers

Rationale: Prepulse inhibition (PPI) of the startle response refers to an a ttenuation in response to a strong stimulus (pulse) if this is preceded sho rtly by a weak non-startling stimulus (prepulse). Patients with schizophren ia have repeatedly been found to show reduced PPI when compared to healthy people. Anticholinergic drugs are often used to control extrapyramidal symp toms induced by antipsychotic medication in schizophrenic patients. Antipsy chotic medication, in particular with atypical drugs, has been shown to imp rove a range of cognitive functions and normalize PPI deficits in schizophr enia, whereas anticholinergic drugs disrupt cognitive functions in both nor mal and schizophrenic populations and also impair PPI in experimental anima ls. No previous study has investigated the effects of anticholinergic drugs on human PPI. Objectives: This study determined the effects of procyclidin e, an anticholinergic drug, on PPI in healthy male volunteers. employing a double-blind placebo-controlled cross-over design. Methods: Subjects underw ent testing for PPI on two occasions: once after the oral administration of a placebo and once after the oral administration of procyclidine in two se parate experiments. Experiment 1 examined the effects of 10 mg procyclidine , whereas experiment 2 examined the effects of 15 mg procyclidine. Results: Procyclidine at a 10 mg dose, as compared to placebo, had no effect on PPI , but caused impairments at a 15 mg dose. In both experiments, procyclidine reduced response amplitude over the pulse-alone trials and heart rate 1-2 h post-administration. Conclusions: PPI of the human acoustic startle respo nse is modulated by procyclidine. The use of anticholinergics needs to be c onsidered in PPI studies in schizophrenia.