Baseline perfusion alterations due to acute application of quetiapine and pramipexole in healthy adults

Abstract

BACKGROUND The dopaminergic system is implicated in many mental processes and neuropsychiatric disorders. Pharmacologically, drugs with dopamine receptor antagonistic and agonistic effects are used, but their effects on functional brain metabolism are not well known. METHODS In this randomized cross-over, placebo-controlled and rater-blinded study, 25 healthy adults received an acute dose placebo substance (starch), quetiapine (dopamine receptor antagonist), or pramipexole (dopamine agonist of the non-ergoline class) 1 hour before the experiment. Background-suppressed 2D pseudo-continuous arterial spin labeling was used to examine whole-brain baseline cerebral blood flow (CBF) differences induced by the three substances. RESULTS We found that quetiapine reduced perfusion in the occipital (early visual areas) and bilateral cerebellar cortex relative to placebo. In contrast, quetiapine enhanced CBF (relative to placebo) in the striatal system (putamen and caudate nucleus) but also in the supplementary motor area (SMA), insular-, prefrontal- as well as in the pre- and postcentral cortex. Pramipexole increased CBF compared to placebo in the caudate nucleus, putamen, middle frontal, SMA, and brainstem (substantia nigra), but reduced CBF in the posterior thalamus, cerebellum, and visual areas. Pramipexole administration resulted in stronger CBF relative to quetiapine in the hypothalamus, cerebellum and substantia nigra. CONCLUSIONS Our results indicate that quetiapine and pramipexole differentially modulate regional baseline CBF. Both substances act on the dopaminergic system, although affecting distinct regions. Quetiapine altered dopaminergic function in frontal, striatal, and motor regions. In contrast, pramipexole affected CBF of the nigrostriatal (striatum and substantia nigra) dopaminergic, but less the fronto-insular system.