NMDA receptor blockade and hippocampal neuronal loss impair fear conditioning and position habit reversal in C57Bl/6 mice.
The interpretation of learning and memory deficits in transgenic mice has largely involved theories of NMDA receptor and/or hippocampal function. However, there is little empirical data that describes what NMDA receptors or the hippocampus do in mice. This research assessed the effects of different doses of the NMDA receptor antagonist, MK-801, or different-sized hippocampal lesions on several behavioral parameters in adult male C57Bl/6 mice. In the first set of experiments, different doses of MK-801 (0.05-0.3mg/kg, s.c.) were assayed in fear conditioning, shock sensitivity, locomotion, anxiety, and position habit reversal tests. Contextual and cued fear conditioning, and position habit reversal were impaired in a dose-dependent manner. Locomotor activity was increased immediately after injection of the highest dose of MK-801. A second set of experiments determined the behavioral effects of a moderate and large excitotoxic hippocampal lesion. Both lesions impaired contextual conditioning, while the larger lesion interfered with cued conditioning. Reversal learning was significantly diminished by the large lesion, while the moderate lesion had a detrimental effect at a trend level (P<0.10). These results provide important reference data for studies involving genetic manipulations of NMDA receptor or hippocampal function in mice. Furthermore, they serve as a basis for a non-transgenic mouse model of the NMDA receptor or hippocampal dysfunction hypothesized to occur in human cognitive disorders.
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110-1093, USA. bardgett@nku.edu
Mark E
ME
Bardgett
Ryan
R
Boeckman
Daniel
D
Krochmal
Hiran
H
Fernando
Rebecca
R
Ahrens
John G
JG
Csernansky
D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000494:pharmacology; D001522:Behavior, Animal; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004597:Electroshock / Q000379:methods; D004924:Escape Reaction / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D006184:Habits; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008124:Locomotion / Q000502:physiology; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D011930:Reaction Time; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012193:Reversal Learning; D014157:Transcription Factors / Q000494:pharmacology
D015214:Antigens, Differentiation, Myelomonocytic; D018691:Excitatory Amino Acid Antagonists; C075373:MNDA protein, human; D016194:Receptors, N-Methyl-D-Aspartate; D014157:Transcription Factors; D016291:Dizocilpine Maleate