Overexpression of alpha2C-adrenoceptors impairs water maze navigation

We investigated the role of overexpression of alpha2C-adrenoceptors in wate r maze navigation in mice transgenically manipulated to have a threefold ov erexpression of the alpha2C-adrenoreceptors. Alpha2C-adrenoreceptors overex pressing mice swam more in the peripheral annulus of the pool and did not f ind the hidden escape platform as well as the wild type control mice. A sub type-nonselective alpha2-adrenoreceptor antagonist, atipamezole (ATI, 1000 mu g/kg, s.c.), fully reversed the deficit in platform finding and search s trategy in overexpressing mice. Noradrenaline depletion (-95%) induced by N -(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) did not impair platform finding of wild type or overexpressing mice. The DSP-4 lesion slightly inc reased swimming in the peripheral annulus in wild type mice, but not in ove rexpressing mice. The DSP-4 lesion produced a dissociable effect on the act ion of atipamezole to improve platform finding and search strategy in overe xpressing mice: atipamezole did not alleviate the platform finding deficit in DSP-4 lesioned overexpressing mice, but normalized their abnormal search strategy. These results suggest that the abnormal search pattern and deficit in the a ccuracy of platform finding are mediated by constitutive activity of overex pressed alpha2C-adrenoreceptors. (C) 1999 IBRO. Published by Elsevier Scien ce Ltd.