Alpha2C-adrenoceptor overexpression disrupts execution of spatial and non-spatial search patterns

We investigated the role of alpha2C-adrenoceptors in the modulation of spatial and non-spatial navigation behaviour. Alpha2C-adrenoceptor overexpressing mice developed an ineffective thigmotaxic search pattern characterized by swimming close to the pool walls during both spatial and non-spatial water maze training. A subtype-nonselective alpha2-adrenoceptor antagonist, atipamezole (1 000 μg/kg, s.c.), fully reversed this impairment in their search strategy. Withdrawal of atipamezole at the end of spatial training resulted in an immediate disruption of the search pattern in alpha2C-adrenoceptor overexpressing mice. The swimming pattern of alpha2C-adrenoceptor overexpressing mice during a five day free swimming period was normal, when no cognitive component was required. Diazepam (0.3 and 1.0 mg/kg, i.p.), on the other hand, did not improve accuracy to find the platform nor decreased thigmotaxis. These results suggest that alpha2C-adrenoceptors may modulate the execution of complex navigation patterns.