Effect of severe neonatal seizures on prepulse inhibition and hippocampal volume of rats tested in early adulthood.

Several lines of evidence indicate that the risk of developing schizophrenia is significantly enhanced following postnatal exposure to environmental insults occurring during the critical periods of early central nervous system development. The hippocampus is a brain structure that has been associated with the neuropathology of schizophrenia. Neonatal epileptic seizures in rat pups can affect the construction of hippocampal networks.

Atypical antipsychotic olanzapine reversed deficit on prepulse inhibition of the acoustic startle reflex produced by microinjection of dizocilpine (MK-801) into the inferior colliculus in rats.

Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. PPI is the normal reduction in the startle response caused by a low intensity non-startling stimulus (prepulse) which is presented shortly before the startle stimulus (pulse). MK-801 is an NMDA receptor-antagonist known to produce hyperactivity, deficits in prepulse inhibition and social withdrawal, behaviors which correlate well with some of the positive, cognitive and negative symptoms of schizophrenia.