Effects of pergolide on sensorimotor gating of the startle reflex in rats.
BACKGROUND
Prepulse inhibition (PPI), a cross-species measure of sensorimotor gating, is impaired in certain neuropsychiatric disorders, including schizophrenia. This study was designed to assess the effects of the D2-family agonist pergolide in rats, in anticipation of human studies of the dopaminergic regulation of PPI.


METHODS
The effects of pergolide (0.0001-0.5 mg/kg) on PPI of the acoustic startle reflex were studied in rats using a wide range of prepulse intensities [1-15 dB(A) over background] and prepulse intervals (5-100 ms, onset to onset). Studies also examined the effects of the D2 antagonist haloperidol on pergolide-induced changes in PPI.


RESULTS
Pergolide exhibited dose- and stimulus-dependent effects on PPI. Pergolide increased PPI when startle stimuli were preceded by weak prepulses [1-5 dB(A) over background] at the longest prepulse interval (100 ms), or intense prepulses [15 dB(A) over background] at short prepulse intervals (5-20 ms). Pergolide (0.5 mg/kg) also decreased PPI elicited by intense prepulses at long intervals (60-100 ms). Both PPI-enhancing and PPI-disruptive effects of pergolide were reversed by the D2 antagonist haloperidol.


CONCLUSIONS
These effects of pergolide suggest that D2 substrates mediate opposing influences on PPI under different stimulus conditions. The dopaminergic regulation of sensorimotor gating appears to interact with stimulus characteristics such as relative intensity and temporal separation, allowing for dynamic shifts in both the quantity and quality of "gated" information.
Swerdlow
N R
NR
Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Dr., La Jolla, CA 92093-0804, USA. nswerdlow@ucsd.edu
Platten
A
A
Shoemaker
J
J
Pitcher
L
L
Auerbach
P
P
D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D008297:Male; D010479:Pergolide / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology
D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D010479:Pergolide