Effects of procyclidine on prepulse inhibition of the acoustic startle response in healthy human volunteers.
BACKGROUND
Prepulse inhibition (PPI) of the startle response refers to an attenuation in response to a strong stimulus (pulse) if this is preceded shortly by a weak non-startling stimulus (prepulse). Patients with schizophrenia have repeatedly been found to show reduced PPI when compared to healthy people. Anticholinergic drugs are often used to control extrapyramidal symptoms induced by antipsychotic medication in schizophrenic patients. Antipsychotic medication, in particular with atypical drugs, has been shown to improve a range of cognitive functions and normalize PPI deficits in schizophrenia, whereas anticholinergic drugs disrupt cognitive functions in both normal and schizophrenic populations and also impair PPI in experimental animals. No previous study has investigated the effects of anticholinergic drugs on human PPI.


OBJECTIVE
This study determined the effects of procyclidine, an anticholinergic drug, on PPI in healthy male volunteers, employing a double-blind placebo-controlled cross-over design.


METHODS
Subjects underwent testing for PPI on two occasions: once after the oral administration of a placebo and once after the oral administration of procyclidine in two separate 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 response is modulated by procyclidine. The use of anticholinergics needs to be considered in PPI studies in schizophrenia.
Kumari
V
V
Section of Cognitive Psychopharmacology, Division of Psychological Medicine Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. v.kumari@iop.kcl.ac.uk
Zachariah
E
E
Galea
A
A
Mehrotra
R
R
Taylor
D
D
Sharma
T
T
D000161:Acoustic Stimulation / Q000379:methods; D000328:Adult; D000339:Affect / Q000187:drug effects* / Q000502:physiology; D000704:Analysis of Variance; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006185:Habituation, Psychophysiologic; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000097:blood / Q000494:pharmacology*; D011352:Procyclidine / Q000097:blood / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology
D018727:Muscarinic Antagonists; D011352:Procyclidine