Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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Neuropsychopharmacology · Jun 1990
A D2 dopamine receptor agonist disrupts sensorimotor gating in rats. Implications for dopaminergic abnormalities in schizophrenia.
Prepulse inhibition of acoustic startle is deficient in schizophrenic patients and in animals injected with either direct or indirect dopamine (DA) agonists. The present experiments confirmed the hypothesis that the dopaminergic blockade of prepulse inhibition is attributable to the activation of D2 DA receptors. After systemic administrations of the D1 agonist SK&F 38393, the D2 agonist quinpirole, or a combination of the two, rats were tested for prepulse inhibition of the startle response by presenting acoustic stimuli or acoustic stimuli preceded by weak prepulses that inhibit startle. ⋯ When an ineffective dose of quinpirole (0.1 mg/kg) was coadministered with 10.0 mg/kg SKF 38393, prepulse inhibition was reduced relative to saline controls. This reduction of prepulse inhibition is consistent with the synergistic effect of D1 and D2 DA receptor stimulation noted in studies of dopaminergic influences on stereotyped behavior in rats. These findings confirm that a disruption of sensorimotor gating results from D2 dopaminergic stimulation in the rat and extend the applicability of this animal model for the similar behavioral deficits exhibited by schizophrenic patients.