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Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism

The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [(11)C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependenc...

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Autores principales: Lingford-Hughes, Anne, Myers, James, Watson, Ben, Reid, Alastair G., Kalk, Nicola, Feeney, Adrian, Hammers, Alexander, Riaño-Barros, Daniela A., McGinnity, Colm J., Taylor, Lindsay G., Rosso, Lula, Brooks, David J., Turkheimer, Federico, Nutt, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Academic Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862962/
https://www.ncbi.nlm.nih.gov/pubmed/26876472
http://dx.doi.org/10.1016/j.neuroimage.2016.02.005
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author Lingford-Hughes, Anne
Myers, James
Watson, Ben
Reid, Alastair G.
Kalk, Nicola
Feeney, Adrian
Hammers, Alexander
Riaño-Barros, Daniela A.
McGinnity, Colm J.
Taylor, Lindsay G.
Rosso, Lula
Brooks, David J.
Turkheimer, Federico
Nutt, David J.
author_facet Lingford-Hughes, Anne
Myers, James
Watson, Ben
Reid, Alastair G.
Kalk, Nicola
Feeney, Adrian
Hammers, Alexander
Riaño-Barros, Daniela A.
McGinnity, Colm J.
Taylor, Lindsay G.
Rosso, Lula
Brooks, David J.
Turkheimer, Federico
Nutt, David J.
author_sort Lingford-Hughes, Anne
collection PubMed
description The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [(11)C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [(11)C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [(11)C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [(11)C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n = 12) underwent an [(11)C]Ro15 4513 PET scan and compared with matched healthy controls (n = 13). We found a significant reduction in [(11)C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [(11)C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [(11)C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [(11)C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates.
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spelling pubmed-48629622016-05-19 Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism Lingford-Hughes, Anne Myers, James Watson, Ben Reid, Alastair G. Kalk, Nicola Feeney, Adrian Hammers, Alexander Riaño-Barros, Daniela A. McGinnity, Colm J. Taylor, Lindsay G. Rosso, Lula Brooks, David J. Turkheimer, Federico Nutt, David J. Neuroimage Article The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [(11)C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [(11)C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [(11)C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [(11)C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n = 12) underwent an [(11)C]Ro15 4513 PET scan and compared with matched healthy controls (n = 13). We found a significant reduction in [(11)C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [(11)C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [(11)C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [(11)C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates. Academic Press 2016-05-15 /pmc/articles/PMC4862962/ /pubmed/26876472 http://dx.doi.org/10.1016/j.neuroimage.2016.02.005 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lingford-Hughes, Anne
Myers, James
Watson, Ben
Reid, Alastair G.
Kalk, Nicola
Feeney, Adrian
Hammers, Alexander
Riaño-Barros, Daniela A.
McGinnity, Colm J.
Taylor, Lindsay G.
Rosso, Lula
Brooks, David J.
Turkheimer, Federico
Nutt, David J.
Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism
title Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism
title_full Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism
title_fullStr Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism
title_full_unstemmed Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism
title_short Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism
title_sort using [(11)c]ro15 4513 pet to characterise gaba-benzodiazepine receptors in opiate addiction: similarities and differences with alcoholism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862962/
https://www.ncbi.nlm.nih.gov/pubmed/26876472
http://dx.doi.org/10.1016/j.neuroimage.2016.02.005
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