Spatial working memory improvement by an α2-adrenoceptor agonist dexmedetomidine is not mediated through α2c-adrenoceptor

1. Aged alpha (2C)-adrenoceptor knockout and wild type mice were used to investigate whether alpha (2C)-adrenoceptors are involved in mediating the beneficial effects Of alpha (2)-adrenoceptor agonist, dexmedetomidine, on spatial working memory. 2. A win-stay task in the radial arm maze was used to dissociate the effects of dexmedetomidine on working vs. reference memory. In addition, the animals were tested in simple response habit learning in the T-maze. 3. Knockout mice made more working memory errors after the change of the baited arm in radial arm maze, but after training reached again as accurate level of performance as wild type controls. Dexmedetomidine 5 and 10 mug/kg alleviated the increase in spatial working memory errors after the change of the baited arm in knockout mice. Knockout and wild type mice performed equally well in T-maze, and dexmedetomidine had no effect on this simple response 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 of alpha (2C)-adrenoceptors is not necessary for the spatial working memory enhancing effect Of alpha (2)-adrenoceptor agonists.