Effects of sustained phencyclidine exposure on sensorimotor gating of startle in rats.

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.

Study at a glance

Abstract

Phencyclidine (PCP), a non-competitive NMDA antagonist with actions at multiple other central nervous system receptors, can cause both acute and lasting psychoses in humans, and has also been used in cross-species models of psychosis. Acute exposure to PCP in rats produces behavioral changes, including a loss of prepulse inhibition (PPI) of the startle reflex, which parallels the loss of PPI observed in schizophrenia patients. Sustained exposure to PCP in rats produces neuropathological changes in several limbic regions and prolonged behavioral abnormalities that may parallel neuropsychological deficits in schizophrenia. It is unclear whether sustained PCP exposure will also produce a loss of prepulse inhibition which parallels the decrease observed in schizophrenia patients. In the present study, we examined changes in PPI during and after sustained PCP administration, using 5-day PCP exposure via subcutaneous osmotic minipumps, or 14-day PCP exposure via repeated intraperitoneal injections. In both forms of drug delivery, PPI was disrupted during, but not after, sustained drug exposure. PPI does not appear to be sensitive to neuropathological effects of sustained PCP exposure.