NMDA antagonists and dopamine agonists produce behavioral and neuropathological changes in rats that may model schizophrenia symptoms. In adult rats, both drug types disrupt sensorimotor gating measured by prepulse inhibition (PPI), mirroring PPI deficits seen in schizophrenia patients. High doses of NMDA antagonists also cause limbic system pathology similar to schizophrenia neuropathology. In 16-day-old rat pups, both the NMDA antagonist phencyclidine (PCP) and the dopamine agonist apomorphine disrupted PPI, showing early developmental functionality of the underlying substrates. However, PCP-induced neurotoxicity was only observed in adult rats, indicating that brain mechanisms responsible for PPI disruption and neurotoxicity are dissociable across development.
Phencyclidine (PCP) can cause acute and lasting psychoses in humans and is used in animal models of psychosis. In rats, acute PCP disrupts prepulse inhibition (PPI) of the startle reflex, similar to deficits seen in schizophrenia. It was unclear whether sustained PCP exposure also disrupts PPI. This study gave rats PCP for 5 days via osmotic minipumps or for 14 days via repeated injections. PPI was disrupted only during drug administration, not after it stopped. PPI does not appear sensitive to the neuropathological effects of sustained PCP exposure.