Effects of bromocriptine and haloperidol on prepulse inhibition of the acoustic startle response in man.
Experiments with animals have shown that D2 dopamine (DA) receptors are involved in prepulse inhibition of the acoustic startle reflex (suppression of the reflex response evoked by a loud sound by prior presentation 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 D2 receptor agonist), haloperidol 3 mg (a D2 receptor antagonist) and combined treatment with bromocriptine 1.25 mg+haloperidol 3 mg, according to a balanced double-blind protocol. Thirty-minute electromyographic recordings from the orbicularis oculi muscle of the right eye were carried out 120 min after ingestion of haloperidol and/or 90 min after ingestion of bromocriptine. Subjects received 36 40-msec sound pulses (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 any of the active treatments. Under the placebo condition, both 75- and 85-dB prepulses inhibited the startle response. Bromocriptine significantly attenuated this prepulse inhibition; haloperidol also produced a small but statistically significant attenuation of prepulse inhibition. Haloperidol significantly antagonized the attenuation of prepulse inhibition produced by bromocriptine. Neither drug altered self-rated alertness, physiological finger tremor, systolic or diastolic blood pressure or salivation. Bromocriptine significantly suppressed and haloperidol significantly elevated serum prolactin levels, these changes being absent when the two drugs were given in combination. The results provide evidence for the involvement of D2 DA receptors in prepulse inhibition of the startle reflex in man.
Abduljawad
K A
KA
Department of Psychiatry, University of Nottingham, Queen's Medical Centre, UK.
Langley
R W
RW
Bradshaw
C M
CM
Szabadi
E
E
D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004311:Double-Blind Method; D006220:Haloperidol / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D011388:Prolactin / Q000097:blood; D013216:Reflex, Startle / Q000187:drug effects*; D012472:Salivation / Q000187:drug effects; D014202:Tremor / Q000139:chemically induced / Q000503:physiopathology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D001971:Bromocriptine; D011388:Prolactin; D006220:Haloperidol