The uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist memantine prolongs spatial memory in a rat delayed radial-arm maze memory task

In the present study, we evaluated the effects of memantine in a delayed radial-arm maze rat task, consisting of an acquisition phase followed 18 h later by a win-shift retrieval test. When administered 20 min before acquisition, memantine elicited an inverted U-shape dose–response relationship, with low doses (0.3 and 0.56 mg/kg) reducing the number of errors committed during the retrieval test, while high doses (3 and 10 mg/kg) disrupted maze running. Memantine given immediately after acquisition or 20 min before retrieval failed to affect performance. Co-administration of subthreshold doses of memantine with either the CB1 receptor antagonist rimonabant or the acetylcholine esterase inhibitor donepezil failed to enhance performance. Thus, low doses of memantine enhance acquisition processes that lead to prolonged spatial memory.