Phencyclidine treatment increases NR2A and NR2B N-methyl-D-aspartate receptor subunit expression in rats.
Administration of noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist phencyclidine to rats on postnatal days 7, 9, and 11 induces apoptosis in prefrontal cortex and hippocampus. In adulthood, these animals display cognitive impairment of working memory, reversal learning and attention that are similar to clinical observations in schizophrenia. In this study, expression of different NMDAR subunits, the postsynaptic mGlu5 receptor and the connecting NMDAR-mGluR5 intracellular postsynaptic density proteins have been measured in adult rats after treatment with phencyclidine on postnatal days 7, 9, and 11. We found that these animals exhibited elevated expression in medial prefrontal cortex of the NR2A and NR2B NMDA receptor subunits in adulthood. These results indicate how behavioral changes in a developmental model for cognitive dysfunction involve changes to specific molecular subsets of the cortical glutamate system.
Research Laboratory for Stereology and Neuroscience, Bispebjerg University Hospital, University of Copenhagen, Denmark.
Sylwia
S
Owczarek
Jack
J
Hou
Thomas
T
Secher
Lars V
LV
Kristiansen
D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity; D005260:Female; D008297:Male; D010622:Phencyclidine / Q000633:toxicity*; D011247:Pregnancy; D016548:Prosencephalon / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D010622:Phencyclidine