title: Effects of Varenicline on Neural Correlates of Alcohol Salience in Heavy Drinkers.
abstract: BACKGROUND
  Preclinical and emerging clinical evidence indicates that varenicline, a nicotinic partial agonist approved for smoking cessation, attenuates alcohol seeking and consumption. Reductions of alcohol craving have been observed under varenicline treatment and suggest effects of the medication on alcohol reward processing, but this hypothesis remains untested.
  
  
  METHODS
  In this double-blind, placebo-controlled randomized experimental medicine study, 29 heavy drinkers underwent a functional magnetic resonance imaging scan after 2 weeks of varenicline (2mg/d) or placebo administration. During functional magnetic resonance imaging, participants performed the Alcohol-Food Incentive Delay task, where they could earn points for snacks or alcohol. At baseline and after 3 weeks of medication, participants underwent intravenous alcohol self-administration sessions in the laboratory.
  
  
  RESULTS
  During the functional magnetic resonance imaging scan, participants in the varenicline group (N=17) reported lower feelings of happiness and excitement on subjective mood scales when anticipating alcohol reward compared with the placebo group (N=12). Linear mixed effects analysis revealed that anticipation of alcohol reward was associated with significant blood oxygen level dependent activation of the ventral striatum, amygdala, and posterior insula in the placebo group; this activation was attenuated in the varenicline group. The varenicline group showed no difference in intravenous alcohol self-administration relative to the placebo group for either session. Participants with higher insula activation when anticipating alcohol reward showed higher alcohol self-administration behavior across groups.
  
  
  CONCLUSIONS
  Our findings suggest that varenicline decreases blood oxygen level dependent activation in striato-cortico-limbic regions associated with motivation and incentive salience of alcohol in heavy drinkers. This mechanism may underlie the clinical effectiveness of varenicline in reducing alcohol intake and indicates its potential utility as a pharmacotherapy for alcohol use disorders.
authors.affiliation: Section on Human Psychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Vatsalya, Gowin, Coe, Cooke, and Ramchandani); Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Schwandt and Heilig); Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Momenan and Hommer); Translational Research Institute, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia (Dr Bartlett).V.V. current affiliation: University of Louisville and Robley Rex VAMC, Louisville, Kentucky.
authors.forename: Vatsalya
authors.initials: V
authors.lastname: Vatsalya
authors.affiliation: Section on Human Psychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Vatsalya, Gowin, Coe, Cooke, and Ramchandani); Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Schwandt and Heilig); Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Momenan and Hommer); Translational Research Institute, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia (Dr Bartlett).V.V. current affiliation: University of Louisville and Robley Rex VAMC, Louisville, Kentucky.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Gowin
authors.affiliation: Section on Human Psychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Vatsalya, Gowin, Coe, Cooke, and Ramchandani); Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Schwandt and Heilig); Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Momenan and Hommer); Translational Research Institute, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia (Dr Bartlett).V.V. current affiliation: University of Louisville and Robley Rex VAMC, Louisville, Kentucky.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Schwandt
authors.affiliation: Section on Human Psychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Vatsalya, Gowin, Coe, Cooke, and Ramchandani); Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Schwandt and Heilig); Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Momenan and Hommer); Translational Research Institute, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia (Dr Bartlett).V.V. current affiliation: University of Louisville and Robley Rex VAMC, Louisville, Kentucky.
authors.forename: Reza
authors.initials: R
authors.lastname: Momenan
authors.affiliation: Section on Human Psychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Vatsalya, Gowin, Coe, Cooke, and Ramchandani); Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Schwandt and Heilig); Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Momenan and Hommer); Translational Research Institute, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia (Dr Bartlett).V.V. current affiliation: University of Louisville and Robley Rex VAMC, Louisville, Kentucky.
authors.forename: Marion A
authors.initials: MA
authors.lastname: Coe
authors.affiliation: Section on Human Psychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Vatsalya, Gowin, Coe, Cooke, and Ramchandani); Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Schwandt and Heilig); Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Momenan and Hommer); Translational Research Institute, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia (Dr Bartlett).V.V. current affiliation: University of Louisville and Robley Rex VAMC, Louisville, Kentucky.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Cooke
authors.affiliation: Section on Human Psychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Vatsalya, Gowin, Coe, Cooke, and Ramchandani); Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Schwandt and Heilig); Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Momenan and Hommer); Translational Research Institute, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia (Dr Bartlett).V.V. current affiliation: University of Louisville and Robley Rex VAMC, Louisville, Kentucky.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Hommer
authors.affiliation: Section on Human Psychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Vatsalya, Gowin, Coe, Cooke, and Ramchandani); Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Schwandt and Heilig); Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Momenan and Hommer); Translational Research Institute, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia (Dr Bartlett).V.V. current affiliation: University of Louisville and Robley Rex VAMC, Louisville, Kentucky.
authors.forename: Selena
authors.initials: S
authors.lastname: Bartlett
authors.affiliation: Section on Human Psychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Vatsalya, Gowin, Coe, Cooke, and Ramchandani); Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Schwandt and Heilig); Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Momenan and Hommer); Translational Research Institute, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia (Dr Bartlett).V.V. current affiliation: University of Louisville and Robley Rex VAMC, Louisville, Kentucky.
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
authors.affiliation: Section on Human Psychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Vatsalya, Gowin, Coe, Cooke, and Ramchandani); Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Schwandt and Heilig); Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Momenan and Hommer); Translational Research Institute, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia (Dr Bartlett).V.V. current affiliation: University of Louisville and Robley Rex VAMC, Louisville, Kentucky. vijayr@mail.nih.gov.
authors.forename: Vijay A
authors.initials: VA
authors.lastname: Ramchandani
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000427:Alcohol Deterrents / Q000627:therapeutic use*; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D059031:Anticipation, Psychological / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D018722:Nicotinic Agonists / Q000627:therapeutic use; D010100:Oxygen / Q000097:blood; D012201:Reward; D012646:Self Administration; D000068580:Varenicline / Q000627:therapeutic use*
chemical_list: D000427:Alcohol Deterrents; D002492:Central Nervous System Depressants; D018722:Nicotinic Agonists; D000431:Ethanol; D010100:Oxygen; D000068580:Varenicline
keywords: Alcohol-Food Incentive Delay (AFID) task; heavy drinkers; intravenous (IV) infusion; neuroimaging; ventral striatum