Pre-training in a radial arm maze abolished anxiety and impaired habituation in C57BL6/J mice treated with dizocilpine

Physiol Behav. 2016 Oct 1;164(Pt A):353-60. doi: 10.1016/j.physbeh.2016.06.017. Epub 2016 Jun 16.

Abstract

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.

Keywords: Anxiety; Familiarity; Habituation; Learning; NMDA; Sensitization.

MeSH terms

  • Animals
  • Anxiety / chemically induced*
  • Anxiety / prevention & control*
  • Avoidance Learning / drug effects
  • Dizocilpine Maleate / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Exploratory Behavior / drug effects
  • Habituation, Psychophysiologic
  • Male
  • Maze Learning* / drug effects
  • Mice, Inbred C57BL
  • Models, Animal
  • Personality
  • Psychological Tests
  • Random Allocation
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Recognition, Psychology / drug effects
  • Resilience, Psychological
  • Spatial Memory / drug effects

Substances

  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate