Baseline Perfusion Alterations Due to Acute Application of Quetiapine and Pramipexole in Healthy Adults.
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 crossover, 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 nonergoline class) 1 hour before the experiment. Background-suppressed 2D pseudo-continuous arterial spin labeling was used to examine whole-brain baseline cerebral blood flow differences induced by the 3 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 cerebral blood flow (relative to placebo) in the striatal system (putamen and caudate nucleus) but also in the supplementary motor area, insular-, prefrontal- as well as in the pre- and postcentral cortex. Pramipexole increased cerebral blood flow compared with placebo in the caudate nucleus, putamen, middle frontal, supplementary motor area, and brainstem (substantia nigra), but reduced cerebral blood flow in the posterior thalamus, cerebellum, and visual areas. Pramipexole administration resulted in stronger cerebral blood flow relative to quetiapine in the hypothalamus, cerebellum, and substantia nigra.


CONCLUSIONS
Our results indicate that quetiapine and pramipexole differentially modulate regional baseline cerebral blood flow. Both substances act on the dopaminergic system, although they affect distinct regions. Quetiapine altered dopaminergic function in frontal, striatal, and motor regions. In contrast, pramipexole affected cerebral blood flow of the nigrostriatal (striatum and substantia nigra) dopaminergic, but less the fronto-insular system.
['Michels|Lars|L|', 'Scherpiet|Sigrid|S|', 'Stämpfli|Philipp|P|', 'Herwig|Uwe|U|', 'Brühl|Annette B|AB|']
D000328:Adult D014150:Antipsychotic Agents D052160:Benzothiazoles D001783:Blood Flow Velocity D001921:Brain D002560:Cerebrovascular Circulation D018592:Cross-Over Studies D018491:Dopamine Agonists D018492:Dopamine Antagonists D059290:Dopaminergic Neurons D005260:Female D064368:Healthy Volunteers D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D008875:Middle Aged D055420:Perfusion Imaging D000077487:Pramipexole D000069348:Quetiapine Fumarate D012039:Regional Blood Flow D013557:Switzerland D013997:Time Factors D055815:Young Adult
quetiapine pramipexole dopamine agonist arterial spin labeling cerebral blood flow dopamine antagonist