Oxytocin plays an important role in the regulation of normal cognitive functions and behaviors, which are disturbed in schizophrenia. Several studies suggest that oxytocinergic function is abnormal in schizophrenia patients. Thus, oxytocin may be involved in the pathophysiology associated with this disorder. This study investigated the regulatory effects of oxytocin on deficits in prepulse inhibition (PPI) associated with schizophrenia. Prepulse inhibition (PPI) is an operational measure of sensorimotor gating which can be measured across many species. PPI is the normal suppression of the startle reflex when the intense startling stimulus ("pulse") is immediately preceded by a weaker stimulus ("prepulse"). Subcutaneously administered oxytocin (0.04-1.0 mg/kg) dose-dependently restored PPI that had been reduced in rats by dizocilpine, a non-competitive NMDA antagonist, and by amphetamine, an indirect dopamine agonist. Oxytocin did not produce a significant effect on baseline PPI or PPI decreased by the direct dopamine agonist, apomorphine. The underlying startle response amplitude was also not significantly altered by oxytocin. These results suggest that oxytocin may play an important role in the modulation of dopaminergic and glutamatergic regulation of PPI, and that it may act as a novel endogenous antipsychotic.