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 proc essing deficits that have been indexed by a number of measures, including d eficits in prepulse inhibition (PPI) of the acoustic startle reflex; and (b ) pathophysiology of the frontal lobe, Recent studies have implicated the p refrontal cortex (PFC) in the modulation of PPI in rats. These studies sugg est that dopamine (DA) ablation of the PFC (using 6-OHDA) leads to disrupti on of PPI. To better understand the role of DA type 1 (D-1) and type 2 (D-2 ) receptors in the modulation of PPI, we investigated the effects of two ph armacologically distinct DA antagonists on the modulation of PPI. Microinje ction of SCH23390 (a D-1 antagonist) into the orbital PFC markedly decrease d PPI (at 0.1, 0.5, and 1.5 mu g), whereas raclopride (a D-2 antagonist) de creased PPI at some doses (0.1 and 0.5 mg/ml) but not at others (5.0 mu g) We conclude that both D-1 and D-2 receptors mediate the cortical modulation of PPI. (C) 1999 Elsevier Science Inc.