Pre-training in a radial arm maze abolished anxiety and impaired habituation in C57BL6/J mice treated with dizocilpine.
Familiarity can imply a reduction of fear and anxiety, which may render learning and memory performance insensitive to NMDA receptor antagonism. Our previous study indicates that MK-801 (dizocilpine), NMDA antagonist, increased anxiety and prevented the acquisition of a spatial memory task. Here, we examined whether MK-801 will produce anxiety in mice that were familiar with the test environment. Male C57BL/6J mice were exposed, one session a day for 7days, to a 3D maze, which consisted of nine arms attached to upward inclined bridges radiating from a nonagonal platform. In this maze, high anxiety mice avoid the arms in the first sessions. One group of mice received saline (SAL) while a second group received MK-801 (MKD1), both on day one. A third group received saline in the first 3 sessions, and MK 801 in subsequent sessions (MKD4). Saline and MK-801 (0.1mg/kg) were administered intraperitoneally 30min before the test. MKD4 mice demonstrated an increase in bridge and arm visits, and reached arm/bridge entries ratio close to 1 in session 5. SAL mice also crossed frequently onto the arms, and reached a comparable ratio, but this was achieved with a lower number of arm visits. MKD1 mice demonstrated a reduced number of arm visits in each session compared to SAL and MKD4 mice. Dizocilpine produced anxiety in mice treated from day 1 of the test, but not in those treated from day 4. It also impaired habituation in animals familiar with the test environment; it produced sustained non-habituating hyperactivity.
University of Sunderland, Sunderland Pharmacy School, Sunderland, UK; Durham University, School of Biological and Biomedical Sciences, Durham, UK.
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RM
Abuhamdah
University of Sunderland, Sunderland Pharmacy School, Sunderland, UK; Durham University, School of Biological and Biomedical Sciences, Durham, UK.
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MD
Hussain
Durham University, School of Biological and Biomedical Sciences, Durham, UK.
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PL
Chazot
University of Sunderland, Sunderland Pharmacy School, Sunderland, UK. Electronic address: abdel.ennaceur@gmail.com.
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Ennaceur
D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000517:prevention & control*; D001362:Avoidance Learning / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D006185:Habituation, Psychophysiologic; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010551:Personality; D011581:Psychological Tests; D011897:Random Allocation; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D021641:Recognition, Psychology / Q000187:drug effects; D055500:Resilience, Psychological; D065852:Spatial Memory / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
Anxiety; Familiarity; Habituation; Learning; NMDA; Sensitization