Effects of amisulpride on human resting cerebral perfusion

Abstract

Quantitative neuroimaging studies show that different neuroleptics have similar effects on resting metabolism/perfusion in the basal ganglia, but vary in their effect on the cortex, especially in the prefrontal and temporal lobes. These differences may represent signatures of the action of medication on distinctive receptor combinations. This study seeks to determine the effect on cerebral perfusion at rest of low-dose amisulpride, a neuroleptic with a receptor profile relatively selective to dopaminergic D2-receptors and both antidepressant and antipsychotic efficacy. Continuous arterial spin labelling in a placebo-controlled, double blind, crossover study at steady state of N = 20 healthy male adults. Relative to placebo, amisulpride was associated with extensive and significant cortical decrements in resting perfusion levels, particularly in the prefrontal lobes (p = 0.01, corrected). Decrements spared the basal ganglia, where perfusion was slightly increased. In contrast to earlier reports on other neuroleptics, amisulpride was associated with intense cortical perfusion decrements at rest. These results are consistent with an existing model in which dopaminergic blockade is associated not only with metabolism/perfusion increases in the basal ganglia, but also with decreases in the cerebral cortex that in most neuroleptics are compensated by action on other receptor systems. The selective receptor profile of amisulpride may explain the extensive cortical decrements.