A therapeutic dose of memantine improves the performance of rats in an active place avoidance task under the continuous dissociation of distal room and proximal arena cues

Abstract

Memory is related to the function of N-methyl-D-aspartate (NMDA) receptors. Depending on the dose, NMDA receptor antagonists (such as memantine or MK-801) can impair memory and/or cognitive as well as procedural functions, while they also can prevent the long-term toxic effects of over-excitation of these receptors in pathophysiological processes. There is an unresolved question of whether memantine at low doses could exert an acute pro-cognitive activity. A therapeutic dose of memantine was found to improve short-term spatial memory tested in the alternation version of active place avoidance in a Carousel Maze, whereas no data are available on long-term memory in various versions of place avoidance. In an effort to reconcile this issue, rats were administered memantine (5 mg/kg) 30 min before a training session and trained in two different versions of place avoidance. A control group received saline injections. In an active place avoidance task (hereby referred to as Room+Arena-), this place was fixed to distal room cues, whereas cues from the arena were misleading. Performance thus demanded the on-going segregation of information that engages cognitive coordination. Following the Room+Arena- training, rats were trained in another place avoidance task (hereby referred to as Arena+), which requires focusing on substratal and idiothetic cues from the arena. In this version, a to-be-avoided sector rotated along with the arena in darkness that hid the extramaze cues. The rats given memantine avoided better than the control rats in the Room+Arena- task. In the Arena+ task, both groups had problems with acquiring the task. Subsequently, memantine was withdrawn and both groups relearned Room+Arena- avoidance with a new sector position. In this task, no effect of groups was seen. In conclusion, memantine at a therapeutic dose improved performance in a task that required the segregation of spatial stimuli into coherent subsets.

Keywords: Carousel maze; Cognitive coordination; Memantine; Rats; Spatial place avoidance.