title: Baseline Perfusion Alterations Due to Acute Application of Quetiapine and Pramipexole in Healthy Adults.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Institute of Neuroradiology, University Hospital Zurich, Zurich, Switzerland (Dr Michels); MR-Center, University Children's Hospital Zurich, Zurich, Switzerland (Dr Michels); Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland (Drs Scherpiet, Stämpfli, Herwig, and Brühl); Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK (Dr Brühl). lars.michels@usz.ch.|L.M. and S.S. are shared first authors. lars.michels@usz.ch.
authors.forename: Lars
authors.initials: L
authors.lastname: Michels
authors.affiliation: Institute of Neuroradiology, University Hospital Zurich, Zurich, Switzerland (Dr Michels); MR-Center, University Children's Hospital Zurich, Zurich, Switzerland (Dr Michels); Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland (Drs Scherpiet, Stämpfli, Herwig, and Brühl); Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK (Dr Brühl).|L.M. and S.S. are shared first authors.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Scherpiet
authors.affiliation: Institute of Neuroradiology, University Hospital Zurich, Zurich, Switzerland (Dr Michels); MR-Center, University Children's Hospital Zurich, Zurich, Switzerland (Dr Michels); Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland (Drs Scherpiet, Stämpfli, Herwig, and Brühl); Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK (Dr Brühl).|L.M. and S.S. are shared first authors.
authors.forename: Philipp
authors.initials: P
authors.lastname: Stämpfli
authors.affiliation: Institute of Neuroradiology, University Hospital Zurich, Zurich, Switzerland (Dr Michels); MR-Center, University Children's Hospital Zurich, Zurich, Switzerland (Dr Michels); Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland (Drs Scherpiet, Stämpfli, Herwig, and Brühl); Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK (Dr Brühl).|L.M. and S.S. are shared first authors.
authors.forename: Uwe
authors.initials: U
authors.lastname: Herwig
authors.affiliation: Institute of Neuroradiology, University Hospital Zurich, Zurich, Switzerland (Dr Michels); MR-Center, University Children's Hospital Zurich, Zurich, Switzerland (Dr Michels); Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland (Drs Scherpiet, Stämpfli, Herwig, and Brühl); Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK (Dr Brühl).|L.M. and S.S. are shared first authors.
authors.forename: Annette B
authors.initials: AB
authors.lastname: Brühl
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D052160:Benzothiazoles / Q000008:administration & dosage*; D001783:Blood Flow Velocity; D001921:Brain / Q000098:blood supply*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000008:administration & dosage*; D018492:Dopamine Antagonists / Q000008:administration & dosage*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000502:physiology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D055420:Perfusion Imaging / Q000379:methods; D000077487:Pramipexole; D000069348:Quetiapine Fumarate / Q000008:administration & dosage*; D012039:Regional Blood Flow; D013557:Switzerland; D013997:Time Factors; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D052160:Benzothiazoles; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D000069348:Quetiapine Fumarate; D000077487:Pramipexole
keywords: arterial spin labeling; cerebral blood flow; dopamine agonist; dopamine antagonist; pramipexole; quetiapine