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Drug Alcohol Depend. 2012 Sep 1;125(1-2):60-6. doi: 10.1016/j.drugalcdep.2012.03.016. Epub 2012 Apr 17.

Acute baclofen diminishes resting baseline blood flow to limbic structures: a perfusion fMRI study.

Author information

  • 1Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA. franklin t@mail.trc.upenn.edu

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.

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

PMID:
22513380
[PubMed - indexed for MEDLINE]
PMCID:
PMC3770303
Free PMC Article

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