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Abstract: The effects on memory and learning ability of the Korean herbal medicine, Saenhyetang (SHT), which is consisted of nine herbs, were investigated. Hot water extracts (HWE-SHT) and ethanol extracts (EE-SHT) were used for the studies. It was shown that N-methyl-d-aspartate (NMDA) receptor 2B (NR2B) was increased in the forebrains of SHT-administrated mice (HWE-SHT), leading to enhanced activation of NMDA receptors, facilitating synaptic potentiation in response to stimulation at 10–100Hz. These HWE-SHT-treated mice exhibit superior ability in learning and memory in various behavioral tasks, showing that NR2B is enhanced by HWE-SHT treatment and also is critical in gating the age-dependent threshold for plasticity and memory formation. NMDA receptor-dependent modifications, which were mediated in part by HWE-SHT administration, of synaptic efficacy, therefore, represent a mechanism for associative learning and memory. Results suggest that oriental medical enhancement of NR2B attributes such as intelligence and memory in mammals is feasible. On the other hand, to examine the effects of EE-SHT on the learning and memory in experimental mice, the passive and active avoidance responses were studied. The EE-SHT ameliorated the memory retrieval deficit induced by ethanol, but not other memory impairment in mice. EE-SHT (10, 20mg/100g, p.o.) did not affect the passive avoidance responses of normal mice in the step through and step down tests, the conditioned and unconditioned avoidance responses of normal mice in the shuttle box and lever press performance tests, and the ambulatory activity of normal mice in normal condition. However, EE-SHT was shown to significantly decrease the spontaneous motor activity during the shuttle box test, and also to prolong the sleeping time induced by pentobarbital in mice at 20mg/kg. These results suggest that EE-SHT has an ameliorating effect on memory retrieval impairment and a weak tranquilizing action. [Copyright &y& Elsevier]