The present study compares, using a double-blind, placebo controlled
design the effects of two α2-agonists, clonidine (0.5, 2, and 5 μg/kg)
and guanfacine (7 and 29 μg/kg) on spatial working memory, planning and
attentional set-****fting, functions thought to be dependent on the
central executive of the prefrontal cortex. Blood pressure and the
subjective feeling of sedation were affected equally by clonidine and
guanfacine. The 0.5 μg/kg and 5 μg/kg doses of clonidine disrupted
spatial working memory, but the medium dose had no effect. The 0.5 and 2
μg/kg doses of clonidine increased impulsive responding in the planning
test. The 5 μg/kg dose of clonidine slowed responding at effortful
levels of planning and attentional set-****fting tests. The 29 μg/kg dose
of guanfacine improved spatial working memory and planning. Guanfacine
had no effect on attentional set-****fting. These data indicate that
guanfacine improved planning and spatial working memory, but clonidine
dose-dependently disrupted performance. It is possible that the greater
selectivity of guanfacine for α2A-adrenoceptor subtype may underlie its
differences from clonidine.
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