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Chronic neonatal phencyclidine treatment produces age-related changes in pentylenetetrazol-induced seizures
R Sircar1, J Veliskova, S L Moshe
1Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461.
Insights
Chronic phencyclidine (PCP) administration alters seizure susceptibility in developing rats in an age-dependent manner. Early postnatal PCP exposure increases seizure risk, while later exposure reduces it, with lasting effects into adulthood.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Pharmacology
Background:
- Excitatory amino acids are crucial for brain plasticity during development.
- The impact of blocking N-methyl-D-aspartate (NMDA) receptor channels during development on behavior remains unclear.
Purpose of the Study:
- To investigate the effects of chronic postnatal phencyclidine (PCP) administration on seizure susceptibility.
- To determine the age-dependent and long-term consequences of NMDA receptor blockade during development.
Main Methods:
- Rats received chronic PCP (5 mg/kg) or saline from postnatal days 5-15, 24-34, or 44-54.
- Short-term effects were assessed via pentylenetetrazol (PTZ)-induced seizures at days 21, 40, or 60.
- Long-term effects were evaluated by testing rats treated from days 5-15 for PTZ-induced seizures at days 40 and 60.
Main Results:
- PCP administration during days 5-15 increased seizure susceptibility at day 21.
- PCP administration during days 24-34 attenuated seizure susceptibility at day 40.
- Long-term testing at day 60 revealed reduced seizure incidence and prolonged latencies in rats treated during days 5-15.
- PCP had minimal effect on seizure susceptibility in older rats (days 44-54).
Conclusions:
- Chronic PCP administration impacts PTZ-induced seizure susceptibility in an age-dependent manner.
- Postnatal PCP exposure induces lasting changes in seizure susceptibility that persist into adulthood.
- NMDA receptor blockade during critical developmental periods has significant neurodevelopmental consequences.
Abstract:
Although excitatory amino acids are known to play a critical role in the plasticity of developing brain, the behavioral 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 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-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 (5 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.