Chronic neonatal phencyclidine treatment produces age-related changes in pentylenetetrazol-induced seizures

Ratna Sitcar, Jana Veliskova, Solomon L. Moshe

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)185-191
Number of pages7
JournalDevelopmental Brain Research
Volume81
Issue number2
DOIs
StatePublished - Sep 16 1994

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Phencyclidine
Pentylenetetrazole
Seizures
Therapeutics
Excitatory Amino Acids
Ion Channels
Aspartic Acid

Keywords

  • Epilepsy
  • N-methyl-d-asparatate receptor-channel complex
  • Rat
  • Schizophrenia

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

Cite this

Chronic neonatal phencyclidine treatment produces age-related changes in pentylenetetrazol-induced seizures. / Sitcar, Ratna; Veliskova, Jana; Moshe, Solomon L.

In: Developmental Brain Research, Vol. 81, No. 2, 16.09.1994, p. 185-191.

Research output: Contribution to journalArticle

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abstract = "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.",
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