The αCaMKIIF89G transgenic mice and their littermate controls were subjected to the rotarod test and Morris water maze test. There was no significant difference in motor coordination and ability between these two groups in the rotarod test. In the visible platform test, transgenic mice showed the normal perception, motivation and motor ability. In addition, transgenic mice performed normally in learning and memory in both place navigation training and the 1st spatial probe test. However, compared with wild type mice, transgenic mice spent significantly more time and swam longer distance to reach hidden platform in the 2nd and 3rd day of spatial reversal learning. These results indicate that αCaMKII overexpression in the forebrain can impair spatial reversal learning. The mechanism of the performance deficit may be relevant to disrupted or abolished LTD in the forebrain.