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AUTHORS: Teresa R. Franklin, Ph.D.a, Joshua Shin B.S.a, Kanchana Jagannathan M.S.a, Jesse J. Suh, Psy.D.a, d, John A. Detre, M.D.b, c, Charles P. O'Brien M.D., Ph.D.a, d, Anna Rose Childress, Ph.D.a, d
aDepartment of Psychiatry, University of Pennsylvania, Philadelphia, PA
bDepartment of Radiology, University of Pennsylvania, Philadelphia, PA
cDepartment of Neurology, University of Pennsylvania, Philadelphia, PA
dPhiladelphia VA Medical Center, Philadelphia, PA
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 20 mg dose of baclofen approximately 110 minutes 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.