title: Investigating the effects of norepinephrine α1 receptor blockade on dopamine levels: A pilot PET study with [11C]-(+)-PHNO in controls.
abstract: Interest in a role for norepinephrine (NE) in substance use disorders has increased over recent years. In particular, its interaction with dopamine (DA) is of importance. In this study, positron emission tomography (PET) was used to explore the impact of prazosin (an alpha 1 NE antagonist) on DA levels. Healthy volunteers were administered prazosin for approximately 4 weeks at the daily dose of 15 mg to reach steady state. Participants were scanned with PET imaging and the [11C]-(+)-PHNO tracer at baseline (before prazosin), at steady state, and after a wash out period. Prazosin administration was associated with an increase of [11C]-(+)-PHNO binding potential in the dorsal caudate relative to baseline, which corresponds to a decrease in DA levels. This study is the first to demonstrate interactions between DA and NE in healthy humans.
authors.affiliation: Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada.|Alcohol Research and Treatment Clinic, Addiction Medicine Services, Ambulatory Care and Structured Treatments, Centre for Addiction and Mental Health, Toronto, Ontario, M6J 1H4, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON, M5S 2S1, Canada.|Department of Family and Community Medicine, University of Toronto, Canada.|Department of Pharmacology, University of Toronto, Canada.|Department of Psychiatry, University of Toronto, Canada.|Division of Brain and Therapeutics, University of Toronto, Canada.|Institute of Medical Sciences, University of Toronto, Canada.
authors.forename: Bernard
authors.identifier: 0000-0002-6406-4973
authors.initials: B
authors.lastname: Le Foll
authors.affiliation: Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada.
authors.forename: Thulasi
authors.initials: T
authors.lastname: Thiruchselvam
authors.affiliation: Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada.
authors.forename: Shawna Xiaoyun
authors.initials: SX
authors.lastname: Lu
authors.affiliation: Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada.
authors.forename: Shakira
authors.initials: S
authors.lastname: Mohammed
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R, Canada.
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Mansouri
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R, Canada.
authors.forename: Dina
authors.initials: D
authors.lastname: Lagzdins
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R, Canada.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R, Canada.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON, M5S 2S1, Canada.|Institute of Medical Sciences, University of Toronto, Canada.|Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R, Canada.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
authors.affiliation: Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Di Ciano
authors.affiliation: Addiction Imaging Research Group, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D001931:Brain Mapping; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D011224:Prazosin / Q000494:pharmacology*; D019275:Radiopharmaceuticals; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D010078:Oxazines; D019275:Radiopharmaceuticals; D018340:Receptors, Adrenergic, alpha-1; C042631:naxagolide; D004298:Dopamine; D011224:Prazosin
keywords: PET; [11C]-(+)-PHNO; dopamine; noradrenaline; prazosin