Memantine ameliorates learning and memory disturbance and the behavioral and psychological symptoms of dementia in thiamine-deficient mice.

Several studies have reported on the beneficial effects of memantine on behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease. However, the effects of memantine on BPSD-like behaviors in animals have not been well addressed. Here, the effects of memantine on memory disturbance and BPSD-like behaviors were evaluated in thiamine-deficient (TD) mice. Memantine (3 and 10 mg/kg, b.i.d.) was orally administered to ddY mice fed a TD diet for 22 days. During the treatment period, the forced swimming test, elevated plus-maze test, passive avoidance test, and locomotor activity test were performed. Neurotransmitter levels in the brain were analyzed after the treatment period. Daily oral administration of memantine ameliorated the memory disturbances, anxiety-like behavior, and depression-like behavior observed in TD mice. Memantine did not have a significant effect on monoamine levels, but increased glutamate levels in the hippocampus in TD mice. These results suggest that memantine prevents or suppresses the progression of BPSD-like behaviors that develop due to TD. This effect may be mediated in part by the enhancement of glutamatergic neuron activity in the hippocampus.