Long-term effects of developmental PCP administration on sensorimotor gating in male and female rats

Rationale Acutely administered N-methyl-D-asparate (NMDA) antagonists are used to model schizophrenia, as measured by impairments in sensorimotor gating reflected in decreases in prepulse inhibition of the startle response (PPI). Aspects of acute NMDA receptor antagonism limit the applications of these models. Objective The aim of this paper is to determine the long-term effects of developmental phencyclidine (PCP) treatment on sensorimotor gating in both male and female rats. Materials and methods Male and female Sprague Dawley rats were injected with PCP (10 mg/kg s.c.) on postnatal days (PN) 7, 9, and 11 and were tested for PPI on PN 32-34. The groups were then divided and some of the animals received a single dose of PCP (10 mg/kg s.c.) on PN 45. The animals were tested again for PPI at approximately 1, 4, and 6 weeks after the treatment. Results There were no significant effects of neonatal-only treatment. One week after the PN 45 treatment, animals that were treated as neonates and as adolescents (PCP/PCP) were significantly impaired in PPI in both sexes. Male and female PCP/PCP rats also had significant increases in acoustic startle response 4 weeks posttreatment, which subsequently declined. PPI impairments in both sexes recovered over time and the adolescent-only treated females showed significant increases (improvement) in PPI approximately 6 weeks posttreatment. Conclusion These data suggest that treatment with an NMDA receptor antagonist during adolescence or early adulthood can produce a relatively long-term impairment of PPI (approximately 1 week) and that this effect is more pronounced in male animals.