title: Acute effects of single-dose aripiprazole and haloperidol on resting cerebral blood flow (rCBF) in the human brain.
abstract: Antipsychotic drugs act on the dopaminergic system (first-generation antipsychotics, FGA), but some also directly affect serotonergic function (second-generation antipsychotics, SGA) in the brain. Short and long-term effects of these drugs on brain physiology remain poorly understood. Moreover, it remains unclear whether any physiological effect in the brain may be different for FGAs and SGAs. Immediate (+3.30 h) and different effects of single-dose FGA (haloperidol, 3 mg) and a SGA (aripiprazole, 10 mg) on resting cerebral blood flow (rCBF) were explored in the same 20 healthy volunteers using a pulsed continuous arterial spin labeling (pCASL) sequence (1.5T) in a placebo-controlled, repeated measures design. Both antipsychotics increased striatal rCBF but the effect was greater after haloperidol. Both decreased frontal rCBF, and opposite effects of the drugs were observed in the temporal cortex (haloperidol decreased, aripiprazole increased rCBF) and in the posterior cingulate (haloperidol increased, aripiprazole decreased rCBF). Further increases were evident in the insula, hippocampus, and anterior cingulate after both antipsychotics, in the motor cortex following haloperidol and in the occipital lobe the claustrum and the cerebellum after aripiprazole. Further decreases were observed in the parietal and occipital cortices after aripiprazole. This study suggests that early and different rCBF changes are evident following a single-dose of FGA and SGA. The effects occur in healthy volunteers, thus may be independent from any underlying pathology, and in the same regions identified as structurally and functionally altered in schizophrenia, suggesting a possible relationship between antipsychotic-induced rCBF changes and brain alterations in schizophrenia.
authors.affiliation: Department of Psychosis Studies, King's College London, Institute of Psychiatry, United Kingdom. rowena.handley@kcl.ac.uk
authors.forename: Rowena
authors.initials: R
authors.lastname: Handley
authors.forename: Fernando O
authors.initials: FO
authors.lastname: Zelaya
authors.forename: A A T Simone
authors.initials: AA
authors.lastname: Reinders
authors.forename: Tiago Reis
authors.initials: TR
authors.lastname: Marques
authors.forename: Mitul A
authors.initials: MA
authors.lastname: Mehta
authors.forename: Ruth
authors.initials: R
authors.lastname: O'Gorman
authors.forename: David C
authors.initials: DC
authors.lastname: Alsop
authors.forename: Heather
authors.initials: H
authors.lastname: Taylor
authors.forename: Atholl
authors.initials: A
authors.lastname: Johnston
authors.forename: Steve
authors.initials: S
authors.lastname: Williams
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
authors.forename: Carmine M
authors.initials: CM
authors.lastname: Pariante
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: Paola
authors.initials: P
authors.lastname: Dazzan
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D000068180:Aripiprazole; D001794:Blood Pressure / Q000187:drug effects; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D011595:Psychomotor Agitation / Q000523:psychology; D015363:Quinolones / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D000068180:Aripiprazole; D006220:Haloperidol