title: Acute baclofen diminishes resting baseline blood flow to limbic structures: a perfusion fMRI study.
abstract: BACKGROUND
  Preclinical and clinical evidence show that the GABA B agonist, baclofen is a promising treatment for addictive disorders; however, until recently its mechanism of action in the human brain was unknown. In previous work we utilized a laboratory model that included a medication versus placebo regimen to examine baclofen's actions on brain circuitry. Perfusion fMRI [measure of cerebral blood flow (CBF)] data acquired 'at rest' before and on the last day of the 21-day medication regimen showed that baclofen diminished CBF bilaterally in the VS, insula and medial orbitofrontal cortex (mOFC). In the present study, we hypothesized that a single dose of baclofen would have effects similar to repeated dosing.
  
  
  METHODS
  To test our hypothesis, in a crossover design, CBF data were acquired using pseudo continuous arterial spin labeled (pCASL) perfusion fMRI. Subjects were either un-medicated or were administered a 20mg dose of baclofen approximately 110 min prior to scanning.
  
  
  RESULTS
  Acute baclofen diminished mOFC, amygdala, and ventral anterior insula CBF without causing sedation (family-wise error corrected at p=0.001).
  
  
  CONCLUSIONS
  Results demonstrate that similar to repeated dosing, an acute dose of baclofen blunts the 'limbic' substrate that is hyper-responsive to drugs and drug cues. Smokers often manage their craving and can remain abstinent for extended periods after quitting, however the risk of eventual relapse approaches 90%. Given that chronic medication may not be a practical solution to the long-term risk of relapse, acute baclofen may be useful on an 'as-needed' basis to block craving during 'at risk' situations.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA. franklin t@mail.trc.upenn.edu
authors.forename: Teresa R
authors.initials: TR
authors.lastname: Franklin
authors.forename: Joshua
authors.initials: J
authors.lastname: Shin
authors.forename: Kanchana
authors.initials: K
authors.lastname: Jagannathan
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Suh
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: D000293:Adolescent; D000328:Adult; D001418:Baclofen / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016000:Cluster Analysis; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008032:Limbic System / Q000098:blood supply* / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D012201:Reward; D016540:Smoking Cessation; D013113:Spin Labels; D055815:Young Adult
chemical_list: D018755:GABA Agonists; D013113:Spin Labels; D001418:Baclofen