The Journal of Neuroscience, July 1, 1999, 19(13):5644-5653
Rat Strain Differences in the Ability to Disrupt Sensorimotor
Gating Are Limited to the Dopaminergic System, Specific to Prepulse
Inhibition, and Unrelated to Changes in Startle Amplitude or Nucleus
Accumbens Dopamine Receptor Sensitivity
Gene G.
Kinney,
Lynn O.
Wilkinson,
Kay L.
Saywell, and
Mark D.
Tricklebank
Merck Sharp and Dohme Research Laboratories, Neuroscience Research
Centre, Harlow, Essex, CM 20 2QR United Kingdom
Previous studies indicate that a variety of pharmacological agents
interfere with the prepulse inhibition of the acoustic startle (PPI)
response including phencyclidine (PCP),
8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), amphetamine, and apomorphine. Strain differences have been observed in the ability of apomorphine to disrupt PPI, although the degree to which these strain differences occur after administration of nondopaminergic drugs or the degree to which differences can be observed in other models of dopamine (DA) receptor activation has not been elucidated. The present study tested the effects of apomorphine, amphetamine, 8-OH-DPAT, and PCP on PPI in the
Sprague Dawley and Wistar rat strains. Because apomorphine disrupts PPI
via activation of DA receptors in the nucleus accumbens, apomorphine-induced hyperlocomotion, also a behavioral model of nucleus
accumbens DA receptor activation, was measured in both rat strains.
Administration of PCP or 8-OH-DPAT attenuated PPI in both strains,
whereas apomorphine and amphetamine only attenuated PPI in Wistar rats.
The ability of apomorphine to increase motor activity in the absence of
a startle-eliciting stimulus was similar in the two strains, as was
apomorphine-induced hyperlocomotion. A time course analysis of the
effects of apomorphine on startle response in Sprague Dawley rats found
that changes in the magnitude of PPI followed changes in basic startle
amplitude. Similarly, no apomorphine-induced attenuation of PPI was
observed in Sprague Dawley rats after 6-OHDA-induced DA
receptor supersensitivity in the nucleus accumbens. These data suggest
a dissociation between the effects of DA receptor agonists in PPI and
other behavioral models of DA receptor activation.
Key words:
amphetamine; apomorphine; phencyclidine; 8-OH-DPAT; prepulse inhibition; dopamine; motor behavior; schizophrenia; rats; startle
Copyright © 1999 Society for Neuroscience 0270-6474/99/19135644-10$05.00/0