title: Varenicline-Induced Elevation of Dopamine in Smokers: A Preliminary [(11)C]-(+)-PHNO PET Study.
abstract: Varenicline, a nicotinic partial agonist, is the most effective treatment for tobacco use disorder. However, its mechanism of action is still unclear and may involve stimulating dopaminergic transmission. Here we used PET imaging with [(11)C]-(+)-PHNO to explore for the first time the impact of varenicline on dopamine transmission in the D2-rich striatum and D3-rich extra-striatal regions and its relationship with craving, withdrawal and smoking. Eleven treatment-seeking smokers underwent two PET scans with [(11)C]-(+)-PHNO, each following 12-h overnight smoking abstinence both prior to receiving varenicline and following 10-11 days of varenicline treatment (ie, at steady-state drug levels). Subjective measures of craving and urges to smoke were also assessed on the days of the PET scans. Varenicline treatment significantly reduced [(11)C]-(+)-PHNO binding in the dorsal caudate (p=0.008) and reduced some craving measures. These findings provide the first evidence that varenicline is able to increase DA levels in the human brain, a factor that may contribute to its therapeutic efficacy.
authors.affiliation: Translational Addiction Research Laboratory, CAMH, Toronto, ON, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Di Ciano
authors.affiliation: Translational Addiction Research Laboratory, CAMH, Toronto, ON, Canada.
authors.forename: Mihail
authors.initials: M
authors.lastname: Guranda
authors.affiliation: Translational Addiction Research Laboratory, CAMH, Toronto, ON, Canada.
authors.forename: Dina
authors.initials: D
authors.lastname: Lagzdins
authors.affiliation: Pharmacogenetics Laboratory, CAMH, Toronto, ON, Canada.|Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Campbell Family Mental Health Research Institute, CAMH, Toronto, ON, Canada.
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
authors.affiliation: Translational Addiction Research Laboratory, CAMH, Toronto, ON, Canada.|Institute of Environmental Studies and Research, Ain Shams University, Cairo, Egypt.
authors.forename: Islam
authors.initials: I
authors.lastname: Gamaleddin
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Ambulatory Care and Structured Treatment Program, CAMH, Toronto, ON, Canada.|Dalla Lana School of Public Health, Toronto, ON, Canada.|Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.|Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Selby
authors.affiliation: Campbell Family Mental Health Research Institute, CAMH, Toronto, ON, Canada.|Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.|Addiction Imaging Group, Research Imaging Centre, CAMH, Toronto, ON, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
authors.affiliation: Translational Addiction Research Laboratory, CAMH, Toronto, ON, Canada.|Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Campbell Family Mental Health Research Institute, CAMH, Toronto, ON, Canada.|Ambulatory Care and Structured Treatment Program, CAMH, Toronto, ON, Canada.|Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.|Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Le Foll
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000032:analysis* / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D050637:Receptors, Dopamine D3 / Q000187:drug effects / Q000502:physiology; D012907:Smoking / Q000503:physiopathology / Q000628:therapy*; D061485:Tobacco Use Cessation Devices; D000068580:Varenicline / Q000494:pharmacology*
chemical_list: C581293:DRD2 protein, human; C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D004298:Dopamine; D000068580:Varenicline