Effects of single oral administrations of haloperidol and d-amphetamine onprepulse inhibition of the acoustic startle reflex in healthy male volunteers

The effects of acute administration of an indirect dopamine-agonist, d-amph etamine, and a non-selective dopamine receptor antagonist, haloperidol, wer e investigated in normal male volunteers on habituation and prepulse inhibi tion (PPI) of the acoustic startle reflex in two experiments. In Experiment 1, 40 male non smoker volunteers were tested for habituation and PPI (defi ned as percentage reduction of the pulse-alone amplitude; prepulses 9 dB ab ove background) before and after double-blind administration of either 2 mg haloperidol or placebo. No influence of haloperidol was observed on either habituation or PPI of the startle reflex in this experiment. In Experiment 2, 60 male volunteers underwent startle testing before and after double-bl ind administration of a single oral dose of 5 mg haloperidol, 5 mg d-amphet amine or placebo. Habituation and PPI (prepulses 15 dB above background) fo r the placebo group did not differ significantly from that observed for the d-amphetamine or for the haloperidol group. However, in a subgroup of smok ing subjects, both d-amphetamine and haloperidol reduced PPI as compared to that observed prior to drug administration. The implications of these find ings in relation to animal pharmacological studies and observed sensorimoto r gating deficits in schizophrenia are discussed. Behav Pharmacol 1998; 9:5 67-576 (C) 1998 Lippincott Williams & Wilkins.