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Title
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Lower limbic metabotropic glutamate receptor 5 availability in alcohol dependence
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Author
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Abstract
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| Animal studies suggest an important role for the metabotropic glutamate receptor subtype 5 (mGlu5) in the pathophysiology of alcohol dependence, but direct human evidence is lacking. The goal of this study was to investigate cerebral mGlu5 availability in alcohol-dependent subjects versus controls using F-18-3-fluoro-5-[(pyridin-3-yl) ethynyl] benzonitrile (F-18-FPEB) PET. Methods: Dynamic 90-min F-18-FPEB scans combined with arterial blood sampling were acquired for 16 recently abstinent alcohol-dependent subjects and 32 age-matched controls. Regional mGlu5 availability was quantified by the F-18-FPEB total distribution volume using both a voxel-by-voxel and a volume-of-interest analysis with partial-volume effect correction. Alcohol consumption within the last 3 mo was assessed by questionnaires and by hair ethyl glucuronide analysis. Craving was assessed using the Desire for Alcohol Questionnaire. Results: mGlu5 availability was lower in mainly limbic regions of alcohol-dependent subjects than in controls (P < 0.05, familywise error-corrected), ranging from 14% in the posterior cingulate cortex to 36% in the caudate nucleus. Lower mGlu5 availability was associated with higher hair ethyl glucuronide levels for most regions and was related to a lower level of craving specifically in the middle frontal gyrus, cingulate cortex, and inferolateral temporal lobe. Conclusion: These findings provide human in vivo evidence that limbic mGlu5 has a role in the pathophysiology of alcohol dependence, possibly involved in a compensatory mechanism helping to reduce craving during abstinence. |
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Language
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English
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Source (journal)
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The Journal of nuclear medicine. - New York
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Publication
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New York
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2018
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ISSN
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0161-5505
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DOI
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10.2967/JNUMED.117.199422
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Volume/pages
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59
:4
(2018)
, p. 682-690
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ISI
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000428981100035
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Pubmed ID
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29348321
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Full text (Publisher's DOI)
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