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.
journal_name
Drug Alcohol Dependjournal_title
Drug and alcohol dependenceauthors
Franklin TR,Shin J,Jagannathan K,Suh JJ,Detre JA,O'Brien CP,Childress ARdoi
10.1016/j.drugalcdep.2012.03.016subject
Has Abstractpub_date
2012-09-01 00:00:00pages
60-6issue
1-2eissn
0376-8716issn
1879-0046pii
S0376-8716(12)00105-6journal_volume
125pub_type
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