The increased dopamine and serotonin were suggested [Niimi et al., 2008. Emotional behavior and expression pattern of tyrosine hydroxylase and tryptophan hydroxylase in senescence-accelerated mouse (SAM) P6 mice. Behav. Brain Res. 188, 329-336], and as these monoamines are well known to influence working memory processes, SAMP6 may show improved working memory. We found that spatial Y-maze memory and non-spatial novel object recognition memory of SAMP6 were improved compared with those of senescence-accelerated mouse resistant 1 (SAMR1). Among molecules known to be related with memory processes other than dopamine and serotonin, we focused on N-methyl-d-aspartate (NMDA) receptors. Animals treated with (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a NMDA receptor antagonist, were subjected to the Y-maze and novel object recognition tests to examine whether NMDA receptors are associated with the improved short-term memory of SAMP6. CPP (10 mg/kg) significantly impaired the spontaneous alternation behavior and the exploratory preference of SAMR1, whereas no significant effect was seen in SAMP6 in either of these behavioral tests. Western blot analyses revealed increased expression of NMDA receptor (NR) subunit 2B in forebrain of SAMP6 compared with SAMR1, while there was no difference in the levels of NR1 and NR2A between SAMR1 and SAMP6. Our results indicate that increased expression of NR2B in forebrain of SAMP6 is one of the causes of the improved short-term memory of SAMP6.
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