期刊
NEUROSCIENCE LETTERS
卷 503, 期 1, 页码 68-72出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2011.08.012
关键词
Brain microdialysis; Cognition; MK-801; NMDA receptor; Rat; Water maze
The non-competitive N-methyl-n-aspartate (NMDA) receptor antagonist (+)MK-801 is widely used in animal research (over 3000 publications), however its extracellular brain concentration has never been reported. Here, we show using in vivo microdialysis that systemic injection of (+)MK-801 at doses of 0.05, 0.1 or 0.2 mg/kg resulted in peak brain ECF concentration of 6, 14 or 34 nM, respectively. Moreover, (+)MK-801 resulted in a dose-dependent learning impairment in the Morris water maze as well as hyperactivity in the open field. These data demonstrate for the first time that (+)MK-801 at doses producing behavioural alterations expected from NMDA receptor blockade reaches extracellular brain concentrations corresponding to the affinity at NMDA receptors. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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