Effects of repeated treatment of phencyclidine on cognition and sensorimotor gating in female C57BL/6 mice of different ages

Abstract

Many studies have indicated that glutamatergic N‐methyl‐D‐aspartate (NMDA) neurotransmission is disturbed in schizophrenia. Phencyclidine (PCP), a NMDA receptor antagonist, can reproduce schizophrenia‐like symptoms in both humans and rodents. This present study investigated the behavioural performances of mice at different ages after repeated administration of high doses of PCP and possible changes of brain apoptotic regulation proteins. 2‐ and 6‐month‐old female C57Bl/6J mice received daily i.p. doses of PCP (20 mg/kg) or saline for 7 d. Testing was performed 24 h after the last day of treatment. Both age groups treated with PCP produced similar impairments in spatial working memory performed in the Y‐maze task and sensorimotor gating deficits in a prepulse inhibition (PPI) task. After behavioural tests, mice were decapitated for western blot analyses. PCP treatment altered the ratio of an anti‐apoptotic Bcl‐2 family member (Bcl‐2) to a proapoptotic analogue (Bax) in the frontal cortex. Our results demonstrate that age does not alter the behavioural sensitivity of mice to the high doses of PCP treatment and PCP‐induced cognitive and sensorimotor gating deficits in mice might be associated with the alterations in the ratio of anti‐apoptotic/proapoptotic proteins. These results suggest that the high‐dose PCP model may have significant potential in characterizing the behavioural and molecular mechanisms underlying cognitive deficits seen in schizophrenia patients.