Prepulse inhibition refers to the inhibition by a weak prepulse of the startle response to an intense stimulus. Prepulse inhibition is thought to provide an operational measure of sensorimotor gating, a putative central inhibitory process by which an organism filters information from its environment. Prepulse inhibition deficits are observed in schizophrenia patients and in rats treated with psychotomimetic compounds, such as the non-competitive N-methyl-D-aspartate antagonists phencyclidine or dizocilpine maleate. In rats, phencyclidine-induced prepulse inhibition deficits are blocked by clozapine, olanzapine and quetiapine, which are multireceptor antagonists and atypical antipsychotics, or by prazosin, which is a selective alpha1-adrenergic antagonist. The dorsal hippocampus and amygdala are two of the brain regions shown to contribute to the disruption of prepulse inhibition produced by non-competitive N-methyl-D-aspartate antagonists. The present study tested the hypotheses that quetiapine or prazosin would prevent deficits in prepulse inhibition produced by dizocilpine infusion into the dorsal hippocampus or amygdala. In separate groups of rats, either quetiapine (0 or 5.0 mg/kg, s.c.) or prazosin (0 or 1.0 mg/kg, i.p.) was administered 15 min prior to bilateral infusion of dizocilpine (0 or 6.25 microg/0.5 microl/side) into either the dorsal hippocampus or amygdala. Rats were placed into startle chambers immediately after intracerebral drug infusion and prepulse inhibition was assessed. Confirming previous studies, prepulse inhibition was decreased after either intra-dorsal hippocampus or intra-amygdala infusions of dizocilpine. Both quetiapine and prazosin blocked the prepulse inhibition deficits produced by intracranial dizocilpine administration. Startle reactivity was increased by dizocilpine infusion into either region; these effects were not blocked by either quetiapine or prazosin. These results indicate that non-competitive N-methyl-D-aspartate antagonists may disrupt sensorimotor gating via actions within the dorsal hippocampus or amygdala, and that alpha1-adrenergic receptors distal to these sites might mediate this effect.