Dopamine antagonists in the orbital prefrontal cortex reduce prepulse inhibition of the acoustic startle reflex in the rat.

Schizophrenia is characterized by, among other things, (a) information processing deficits that have been indexed by a number of measures, including deficits in prepulse inhibition (PPI) of the acoustic startle reflex; and (b) pathophysiology of the frontal lobe. Recent studies have implicated the prefrontal cortex (PFC) in the modulation of PPI in rats. These studies suggest that dopamine (DA) ablation of the PFC (using 6-OHDA) leads to disruption of PPI. To better understand the role of DA type 1 (D1) and type 2 (D2) receptors in the modulation of PPI, we investigated the effects of two pharmacologically distinct DA antagonists on the modulation of PPI. Microinjection of SCH23390 (a D1 antagonist) into the orbital PFC markedly decreased PPI (at 0.1, 0.5, and 1.5 microg), whereas raclopride (a D2 antagonist) decreased PPI at some doses (0.1 and 0.5 mg/ml) but not at others (5.0 microg). We conclude that both D1 and D2 receptors mediate the cortical modulation of PPI.