Low-dose memantine induced working memory improvement in the allothetic place avoidance alternation task (APAAT) in young adult male rats

Working memory combines newly acquired information, cognitive skill learning and executive function. Its functioning dependent on NMDA receptors, which are involved in neuronal plasticity. To assess their role simultaneously in spatial working memory and non-cognitive learning, we used NMDAR antagonists, memantine and MK-801, and the Allothetic Place Avoidance Alternation Task (APAAT). In this test rats should avoid entering a place where shocks were presented on a rotating arena which requires cognitive coordination for the segregation of stimuli, the relevant from room and misleading from the arena. Over three consecutive days the rats underwent habituation, avoidance training (with shocks), and a retrieval test. The shock place was alternated daily. The after-effects of the agents were tested on Day21. Rats treated with low dose of memantine improved working memory and cognitive skill (the shocks/entrances ratio). Animals treated with high doses of MK-801 and memantine presented impairment of memory and enhancement of locomotor activity. On D21 rats treated by high dose of MK-801 performed the memory task better than the high memantine rats, whereas the rats’ activity depended on condition, not on the group factor. These results suggest that in naive rats mild NMDAR blockade by low-dose memantine improves working memory related to a highly challenging task.


13 May 2014