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 CB 1 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.