Repeated treatment with N-methyl-d-aspartate antagonists in neonatal, but not adult, rats causes long-term deficits of radial-arm maze learning.
Brain glutamatergic system is involved in synaptic plasticity as a base for learning and neural development. This study investigated the effects of neonatal and adult chronic antagonism of N-methyl-d-aspartate (NMDA) receptors, a subtype of glutamate receptors, on learning and/or memory. Rats were trained in the radial-maze learning, which is known as a measure of spatial working memory capacities, in adulthood after neonatal or adult repeated treatment of MK-801 (dizocilpine; 5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine), a non-competitive antagonist, or neonatal repeated treatment of CGS 19755 (cis-4-phosphonomethyl-2-piperadine carboxilic acid), a competitive antagonist. Neonatal repeated treatment of MK-801 or CGS 19755 markedly impaired the radial-arm maze learning. In addition, the treatment altered activities differently in the radial-maze and in the open-field. On the other hand, adult repeated treatment with MK-801 affected neither the radial-maze learning nor activities. Results suggest that chronic blockade of NMDA receptors in a neonatal stage may produce long-lasting deteriorative effects on spatial working memory in adulthood.
Kawabe
Kouichi
K
Graduate School of Literature and Human Sciences, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
Iwasaki
Tsuneo
T
Ichitani
Yukio
Y
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007859:Learning Disabilities / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D010875:Pipecolic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013995:Time
D018691:Excitatory Amino Acid Antagonists; D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C053672:selfotel; D016291:Dizocilpine Maleate