Spatial learning is delayed and brain-derived neurotrophic factor mRNA expression inhibited by administration of MK-801 in rats.
Brain-derived neurotrophic factor (BDNF) is involved in activity-dependent plasticity and interacts with the neurotransmitter glutamate. Glutamate N-methl-D-aspartate (NMDA) receptor activation increases BDNF expression, while BDNF facilitates NMDA activity, with both involved in spatial learning. Administration of the NMDA receptor antagonist MK-801 can impair this leaning. The interaction between NMDA and BDNF in learning is examined in this study. Adult male Sprague-Dawley rats received either i.p. MK-801 or saline and were trained to locate a submerged water maze platform. Sedentary and activity yoked groups were included for biochemical comparisons. Control rats quickly learned the platform location while MK-801-treated rats learned at a significantly slower rate (P < 0.0001). In situ hybridization for hippocampal BDNF mRNA indicated significant increases in the yoked and learning groups. However, MK-801 attenuated the BDNF mRNA increase in the learning and activity-yoked conditions (P < 0.05). Administration of MK-801 to the sedentary group did not alter baseline mRNA levels. These data suggest that BDNF expression is important for NMDA-dependent learning and memory. Interestingly, learning still occurs across trials independent of the NMDA and BDNF interaction. Increases in BDNF and NMDA activity may be significant components in learning and memory, and modulation of these systems may be beneficial for developing strategies to improve cognitive function.
Kesslak
J Patrick
JP
Institute for Brain Aging and Dementia, University of California, Irvine, CA 92697-4540, USA. jpkessla@uci.edu
Chuang
Kenneth R
KR
Berchtold
Nicole C
NC
D000818:Animals; D001921:Brain / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000528:radiation effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects*
D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate