title: Modulation of resting brain cerebral blood flow by the GABA B agonist, baclofen: a longitudinal perfusion fMRI study.
abstract: BACKGROUND
  Preclinical studies confirm that the GABA B agonist, baclofen blocks dopamine release in the reward-responsive ventral striatum (VS) and medial prefrontal cortex, and consequently, blocks drug motivated behavior. Its mechanism in humans is unknown. Here, we used continuous arterial spin labeled (CASL) perfusion fMRI to examine baclofen's effects on blood flow in the human brain.
  
  
  METHODS
  Twenty-one subjects (all smokers, 12 females) were randomized to receive either baclofen (80 mg/day; N=10) or placebo (N=11). A five minute quantitative perfusion fMRI resting baseline (RB) scan was acquired at two time points; prior to the dosing regimen (Time 1) and on the last day of 21 days of drug administration (Time 2). SPM2 was employed to compare changes in RB from Time 1 to 2.
  
  
  RESULTS
  Baclofen diminished cerebral blood flow (CBF) in the VS and mOFC and increased it in the lateral OFC, a region involved in suppressing previously rewarded behavior. CBF in bilateral insula was also blunted by baclofen (T values ranged from -11.29 to 15.3 at p=0.001, 20 contiguous voxels). CBF at Time 2 was unchanged in placebo subjects. There were no differences between groups in side effects or cigarettes smoked per day (at either time point).
  
  
  CONCLUSIONS
  Baclofen's modulatory actions on regions involved in motivated behavior in humans are reflected in the resting state and provide insight into the underlying mechanism behind its potential to block drug-motivated behavior, in preclinical studies, and its putative effectiveness as an anti-craving/anti-relapse agent in humans.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Center for Studies of Addiction and VA Medical Center, Philadelphia, PA, USA. franklin t@mail.trc.upenn.edu
authors.forename: Teresa R
authors.initials: TR
authors.lastname: Franklin
authors.forename: Ze
authors.initials: Z
authors.lastname: Wang
authors.forename: Nathan
authors.initials: N
authors.lastname: Sciortino
authors.forename: Derek
authors.initials: D
authors.lastname: Harper
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hakun
authors.forename: Susan
authors.initials: S
authors.lastname: Kildea
authors.forename: Kyle
authors.initials: K
authors.lastname: Kampman
authors.forename: Ron
authors.initials: R
authors.lastname: Ehrman
authors.forename: John A
authors.initials: JA
authors.lastname: Detre
authors.forename: Charles P
authors.initials: CP
authors.lastname: O'Brien
authors.forename: Anna Rose
authors.initials: AR
authors.lastname: Childress
mesh_terms: D000328:Adult; D001418:Baclofen / Q000009:adverse effects / Q000494:pharmacology*; D001479:Basal Ganglia / Q000187:drug effects; D001921:Brain / Q000098:blood supply* / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D058786:GABA-B Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D010919:Placebos; D017397:Prefrontal Cortex / Q000187:drug effects; D013997:Time Factors; D055815:Young Adult
chemical_list: D058786:GABA-B Receptor Agonists; D010919:Placebos; D001418:Baclofen