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PCP/NMDA receptor-channel complex and brain development

R Sircar1, C S Li

  • 1Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461.

Neurotoxicology and Teratology
|July 1, 1994
PubMed
Summary
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Postnatal exposure to phencyclidine (PCP) in rats alters N-methyl-D-aspartate (NMDA) receptor function. This neurochemical change in developing brains may lead to long-term neurobehavioral consequences.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Developmental Biology

Background:

  • Phencyclidine (PCP) affects multiple neurotransmitter systems, but its psychotomimetic effects occur at lower doses than its impact on these systems.
  • PCP primarily binds to a site within the ionophore of the N-methyl-D-aspartate (NMDA) receptor complex, serving as a marker for NMDA channel activity.
  • The NMDA receptor-channel complex is crucial for brain development, yet the neurochemical effects of postnatal NMDA antagonist administration are not well understood.

Purpose of the Study:

  • To investigate the neurochemical effects of postnatal phencyclidine (PCP) administration on NMDA receptor function in developing rats.
  • To assess alterations in PCP receptor binding following chronic PCP exposure during early development.

Main Methods:

  • Rats were administered PCP daily from postnatal Day 5 to Day 15.

Related Experiment Videos

  • On postnatal Day 21, [3H]MK-801 binding, a specific ligand for the PCP receptor, was measured in rat forebrain.
  • Binding assays were conducted under baseline conditions and in the presence of L-glutamate and glycine.

    • Main Results:

    • Postnatal PCP administration resulted in specific changes to PCP receptor binding in 21-day-old rat forebrain.
    • A reduction in the high-affinity component of [3H]MK-801 binding was observed under baseline conditions.
    • While [3H]MK-801 binding increased significantly from baseline in PCP-treated rats with L-glutamate and glycine, it did not differ from control groups.

    Conclusions:

    • Chronic PCP administration during development alters NMDA channel functioning in rats.
    • These neurochemical alterations suggest potential long-term neurobehavioral consequences.
    • The study highlights the sensitivity of the developing NMDA receptor system to PCP exposure.