Spatial working memory improvement by an alpha(2)-adrenoceptor agonist dexmedetomidine is not mediated through alpha(2c)-adrenoceptor

1. Aged alpha (2C)-adrenoceptor knockout and wild type mice were used to in vestigate whether alpha (2C)-adrenoceptors are involved in mediating the be neficial effects Of alpha (2)-adrenoceptor agonist, dexmedetomidine, on spa tial working memory. 2. A win-stay task in the radial arm maze was used to dissociate the effect s of dexmedetomidine on working vs. reference memory. In addition, the anim als were tested in simple response habit learning in the T-maze. 3. Knockout mice made more working memory errors after the change of the ba ited arm in radial arm maze, but after training reached again as accurate l evel of performance as wild type controls. Dexmedetomidine 5 and 10 mug/kg alleviated the increase in spatial working memory errors after the change o f the baited arm in knockout mice. Knockout and wild type mice performed eq ually well in T-maze, and dexmedetomidine had no effect on this simple resp onse learning, 4. The present results indicate that alpha (2)-adrenoceptor agonists have a selective effect on spatial working memory not only in monkeys but also in mice. Further, this study confirms our earlier finding that the presence o f alpha (2C)-adrenoceptors is not necessary for the spatial working memory enhancing effect Of alpha (2)-adrenoceptor agonists.