EFFECTS OF BROMOCRIPTINE AND HALOPERIDOL ON PREPULSE INHIBITION OF THE ACOUSTIC STARTLE RESPONSE IN MAN

Experiments with animals have shown that D-2 dopamine (DA) receptors a re involved in prepulse inhibition of the acoustic startle reflex (sup pression of the reflex response evoked by a loud sound by prior presen tation of a low-intensity stimulus). The present experiment attempted to extend this observation to man. Twelve healthy males (18-30 years), screened for normal hearing thresholds, participated in four sessions in which they received oral doses of placebo, bromocriptine 1.25 mg ( a D-2 receptor agonist), haloperidol 3 mg (a D-2 receptor antagonist) and combined treatment with bromocriptine 1.25 mg+haloperidol 3 mg, ac cording to a balanced double-blind protocol. Thirty-minute electromyog raphic recordings from the orbicularis oculi muscle of the right eye w ere carried out 120 min after ingestion of haloperidol and/or 90 min a fter ingestion of bromocriptine. Subjects received 36 40-msec sound pu lses (115 dB), separated by variable intervals (mean 25 sec); in 24 of the trials the pulse was preceded by a 40-msec prepulse (75 dB in 12 trials and 85 dB in 12 trials; prepulse-pulse interval, 120 msec). The amplitude of the startle response was not significantly altered by an y of the active treatments. Under the placebo condition, both 75- and 85-dB prepulses inhibited the startle response. Bromocriptine signific antly attenuated this prepulse inhibition; haloperidol also produced a small but statistically significant attenuation of prepulse inhibitio n. Haloperidol significantly antagonized the attenuation of prepulse i nhibition produced by bromocriptine. Neither drug altered self-rated a lertness, physiological finger tremor, systolic or diastolic blood pre ssure or salivation. Bromocriptine significantly suppressed and halope ridol significantly elevated serum prolactin levels, these changes bei ng absent when the two drugs were given in combination. The results pr ovide evidence for the involvement of D-2 DA receptors in prepulse inh ibition of the startle reflex in man.