CONTRASTING EFFECTS OF CLONIDINE AND DIAZEPAM ON TESTS OF WORKING-MEMORY AND PLANNING

The alpha(2) adrenoceptor has recently been implicated in working memo ry (WM), a function dependent on the integrity of the prefrontal corte x. Using a double-blind, placebo-controlled design, the present invest igation examines the effects of two doses (1.5 mu g/kg and 2.5 mu g/kg ) of the mixed alpha(1)/alpha(2) adrenoceptor agonist clonidine (CLO) on performance of various computerised tests of WM and planning in hea lthy, young volunteers. These are compared to the effects produced by two doses (5 mg and 10 mg) of diazepam (DZP) on largely the same set o f neuropsychological tests in a comparable set of subjects. Administra tion of CLO resulted in impulsivity of responding in a planning task, as well as differential dose-dependent effects on two analogous tests of spatial and visual WM. The nature of these effects were suggestive of mnemonic, rather than executive, dysfunction. Conversely, DZP produ ced specific deficits on tests of spatial WM and planning very similar to those seen following lesions to the frontal lobes. Therefore, thes e two sedative drugs produce doubly dissociable, dose-dependent effect s on different aspects of cognitive function.