PCP/NMDA receptor-channel complex and brain development.
Phencyclidine (PCP) acts on a variety of neurotransmitter systems--cholinergic, catechoaminergic, indoleaminergic, and peptidergic--but the dose at which it produces its psychotomimetic effects is lower than the concentration at which it affects these systems. At low doses, PCP interacts primarily with a binding site located within the ionophore associated with the NMDA receptor complex--binding to this site has been used as a biochemical marker for NMDA channel activity. PCP/NMDA receptor-channel complex has been shown to play an important role in brain development but little is known of the neurochemical effects following postnatal administration of NMDA antagonists in rats. In the present study, rats were treated with PCP from Day 5 until Day 15 after birth and binding to the PCP receptor was measured on postnatal Day 21 using [3H]MK-801; MK-801 is a more potent and specific ligand at the PCP receptor than PCP itself. Postnatal PCP administration produced specific alterations in PCP receptor binding in 21-day-old rat forebrain. There was a reduction in the high affinity component of [3H]MK-801 binding under baseline binding conditions. In the presence of both L-glutamate and glycine, [3H]MK-801 binding in PCP-treated rats increased significantly compared to baseline but did not differ from saline-treated controls. These findings suggest that chronic PCP administration in developing rats alter NMDA channel functioning which could have long-term neurobehavioral consequences.
Sircar
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Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461.
Li
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CS
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D005260:Female; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D010622:Phencyclidine / Q000494:pharmacology*; D011247:Pregnancy; D016548:Prosencephalon / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D017478:Receptors, Phencyclidine / Q000502:physiology*
D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D017478:Receptors, Phencyclidine; D016291:Dizocilpine Maleate; D010622:Phencyclidine