CHRONIC NEONATAL PHENCYCLIDINE TREATMENT PRODUCES AGE-RELATED-CHANGESIN PENTYLENETETRAZOL-INDUCED SEIZURES

Although excitatory amino acids are known to play a critical role in t he plasticity of developing brain, the behavioral effects of blocking the N-methyl-D-aspartate (NMDA) receptor-gated ion channel during deve lopment are not clear. Here we report the effects of chronic postnatal administration of 1-phenylcyclohexylpiperidine (phencyclidine or PCP) , a NMDA channel blocker, on seizure susceptibility. To study the shor t-term effects of chronic PCP administration on pentylenetetrazol (PTZ )-induced seizures, rats were treated with PCP (5 mg/kg, i.p.) for 11 days from postnatal days 5-15, 24-34 or 44-54 and tested in the PTZ-in duced seizure paradigm on postnatal days 21, 40 and 60, respectively. Administration of PCP in 5-15-day-old rats resulted in increased seizu re susceptibility at day 21, while administration of PCP in postweanli ng rats (days 24-34) markedly attenuated their susceptibility to seizu res at day 40. PCP injection had little effect on the seizure suscepti bility of older rats. To study the long-term effects of postnatal PCP treatment, rats were injected with PCP (5 mg/kg from postnatal day 5-1 5, i.p.) and were tested for PTZ-induced seizures on postnatal days 40 and 60; each rat was tested only once. When tested for PTZ-induced se izure on day 40, PCP-treated rats did not differ from saline-treated c ontrols. When tested on day 60, PCP-treated rats had a lower incidence of seizures and in the rats that did have seizures their latencies we re significantly prolonged compared to controls. Together, our data su ggest that chronic PCP administration alters PTZ-induced seizure susce ptibility in an age-dependent manner and chronic PCP administration in postnatal rats produces long-term changes that persist into adulthood .