TY - JOUR
T1 - Chronic neonatal phencyclidine treatment produces age-related changes in pentylenetetrazol-induced seizures
AU - Sitcar, Ratna
AU - Veliskova, Jana
AU - Moshe, Solomon L.
N1 - Funding Information:
This research project was supported by the National Institute for Drug Abuse (PHS Grant DA-07188; RS), NIH Grant (NS 20253; SLM) the National Alliance for Research on Schizophrenia and Depression, the National Alliance for the Mentally III (both to RS.) and the Department of Psychiatry, T. Byram Karasu, M.D. Chairman.
PY - 1994/9/16
Y1 - 1994/9/16
N2 - Although excitatory amino acids are known to play a critical role in the plasticity of developing brain, the behavioural effects of blocking the N-methyl-d-aspartate (NMDA) receptor-gated ion channel during development 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 short-term effects of chronic PCP administration on pentylemetetrazol (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-induced seizure paradigm on postnatal days 21, 40 and 60, respectively. Administration of PCP in 5-15-day-old rats resulted in increased seizure susceptibility at day 21, while administration of PCP in postweanling rats (days 24-34) markedly attenuated their susceptibility to seizures at day 40. PCP injection had little effect on the seizure susceptibility of older rats. To study the long-term effects of postnatal PCP treatment, rats were injected with PCP 15 mg/kg from postnatal day 5-15, 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 seizure on day 40, PCP-treated rats did not differ from saline-treated controls. When tested on day 60, PCP-treated rats had a lower incidence of seizures and in the rats that did have seizures their latencies were significantly prolonged compared to controls. Together, our data suggest that chronic PCP administration alters PTZ-induced seizure susceptibility in an age-dependent manner and chronic PCP administration in postnatal rats produces long-term changes that persist into adulthood.
AB - Although excitatory amino acids are known to play a critical role in the plasticity of developing brain, the behavioural effects of blocking the N-methyl-d-aspartate (NMDA) receptor-gated ion channel during development 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 short-term effects of chronic PCP administration on pentylemetetrazol (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-induced seizure paradigm on postnatal days 21, 40 and 60, respectively. Administration of PCP in 5-15-day-old rats resulted in increased seizure susceptibility at day 21, while administration of PCP in postweanling rats (days 24-34) markedly attenuated their susceptibility to seizures at day 40. PCP injection had little effect on the seizure susceptibility of older rats. To study the long-term effects of postnatal PCP treatment, rats were injected with PCP 15 mg/kg from postnatal day 5-15, 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 seizure on day 40, PCP-treated rats did not differ from saline-treated controls. When tested on day 60, PCP-treated rats had a lower incidence of seizures and in the rats that did have seizures their latencies were significantly prolonged compared to controls. Together, our data suggest that chronic PCP administration alters PTZ-induced seizure susceptibility in an age-dependent manner and chronic PCP administration in postnatal rats produces long-term changes that persist into adulthood.
KW - Epilepsy
KW - N-methyl-d-asparatate receptor-channel complex
KW - Rat
KW - Schizophrenia
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U2 - 10.1016/0165-3806(94)90305-0
DO - 10.1016/0165-3806(94)90305-0
M3 - Article
C2 - 7813041
AN - SCOPUS:0027956928
SN - 0165-3806
VL - 81
SP - 185
EP - 191
JO - Developmental Brain Research
JF - Developmental Brain Research
IS - 2
ER -