Postnatal phencyclidine-induced deficit in adult water maze performance is associated with N-methyl-D-aspartate receptor upregulation.
The N-methyl-D-aspartate (NMDA) receptor plays an important role in developmental plasticity. Earlier, we have shown that blocking the NMDA receptor with the non-competitive antagonist phencyclidine (PCP), during a brief postnatal period, disrupts the water maze performance in young juvenile rats (starting at 25 days of age). We now show the long-term effects of postnatal phencyclidine exposure on spatial learning and memory. Male and female rats were exposed to PCP (1 and 5mg/kg) or saline, from postnatal days 5-15, and their performance in the Morris water maze (MWM) was tested both as adolescents (starting on postnatal day (PD) 35) and as adults (starting on postnatal day 60). Separate groups of adult male and female postnatal PCP-treated and saline-treated rats were sacrificed and saturation [3H]MK-801 binding experiments were carried out in their hippocampi and frontal cortices; hippocampus and frontal cortex have high densities of NMDA receptors and both regions are important in spatial learning and memory. Postnatal PCP administration disrupted the water maze performance both in adolescent and adult rats of both sexes. Adult male and female rats treated postnatally with PCP had increased maximal [3H]MK-801 binding in the hippocampus and frontal cortex compared to same-sex saline-treated controls. Taken together, repeated postnatal PCP (RPP) administration impaired the acquisition of spatial learning in adolescent and adult male and female rats, and this cognitive deficit was associated with increased [3H]MK-801 labeled NMDA receptor in the hippocampus and frontal cortex. These findings are consistent with the hypothesis that PCP treatment during the postnatal period produces deficits in the water maze performance by disrupting the developing glutamatergic system.
Sircar
Ratna
R
Laboratory for Developmental Neuroscience, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Forchheimer Building Room 109, Bronx, NY 10461, USA. sircar@aecom.yu.edu
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D010622:Phencyclidine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012153:Retention, Psychology / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D010622:Phencyclidine