Pramipexole effects on startle gating in rats and normal men.
BACKGROUND
Dopamine D3 receptors regulate sensorimotor gating in rats, as evidenced by changes in prepulse inhibition (PPI) of startle after acute administration of D3 agonists and antagonists. In this study, we tested the effects of the D3-preferential agonist, pramipexole, on PPI in normal men and Sprague-Dawley rats.


METHODS
Acoustic startle and PPI were tested in clinically normal men, comparing the effects of placebo vs. 0.125 mg (n = 20) or placebo vs. 0.1875 mg (n = 20) pramipexole, in double blind, crossover designs. These measures were also tested in male Sprague-Dawley rats using a parallel design [vehicle vs. 0.1 mg/kg (n = 8), vehicle vs. 0.3 mg/kg (n = 8) or vehicle vs. 1.0 mg/kg pramipexole (n = 8)]. Autonomic and subjective measures of pramipexole effects and several personality instruments were also measured in humans.


RESULTS
Pramipexole increased drowsiness and significantly increased PPI at 120-ms intervals in humans; the latter effect was not moderated by baseline PPI or personality scale scores. In rats, pramipexole causes a dose-dependent reduction in long-interval (120 ms) PPI, while low doses actually increased short-interval (10-20 ms) PPI. Effects of pramipexole on PPI in rats were independent of baseline PPI and changes in startle magnitude.


CONCLUSIONS
The preferential D3 agonist pramipexole modifies PPI in humans and rats. Unlike indirect DA agonists and mixed D2/D3 agonists, pramipexole increases long-interval PPI in humans, in a manner that is independent of baseline PPI and personality measures. These findings are consistent with preclinical evidence for differences in the D2- and D3-mediated regulation of sensorimotor gating.
Swerdlow
Neal R
NR
Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA. nswerdlow@ucsd.edu
Lelham
Sophia A
SA
Sutherland Owens
Ashley N
AN
Chang
Wei-Li
WL
Sassen
Sebastiaan D T
SD
Talledo
Jo A
JA
D000293:Adolescent; D000328:Adult; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010551:Personality / Q000502:physiology*; D000077487:Pramipexole; D051381:Rats; D017207:Rats, Sprague-Dawley; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D055139:Sensory Gating / Q000187:drug effects* / Q000502:physiology; D012894:Sleep Stages / Q000187:drug effects
D052160:Benzothiazoles; D018491:Dopamine Agonists; D050637:Receptors, Dopamine D3; D000077487:Pramipexole