title: Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism.
abstract: 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.
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, Du Cane Rd., London W12 0NN, United Kingdom; Psychopharmacology Unit, University of Bristol, Whitson Street, Bristol BS1 3NY, United Kingdom; MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom; Hammersmith Imanet Ltd., Hammersmith Hospital, Du Cane Rd., London W12 0NN, United Kingdom. Electronic address: anne.lingford-hughes@ic.ac.uk.
authors.forename: Anne
authors.initials: A
authors.lastname: Lingford-Hughes
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, Du Cane Rd., London W12 0NN, United Kingdom; Psychopharmacology Unit, University of Bristol, Whitson Street, Bristol BS1 3NY, United Kingdom; MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Myers
authors.affiliation: Psychopharmacology Unit, University of Bristol, Whitson Street, Bristol BS1 3NY, United Kingdom; MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom; Hammersmith Imanet Ltd., Hammersmith Hospital, Du Cane Rd., London W12 0NN, United Kingdom.
authors.forename: Ben
authors.initials: B
authors.lastname: Watson
authors.affiliation: Psychopharmacology Unit, University of Bristol, Whitson Street, Bristol BS1 3NY, United Kingdom; MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom; Hammersmith Imanet Ltd., Hammersmith Hospital, Du Cane Rd., London W12 0NN, United Kingdom.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: Reid
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, Du Cane Rd., London W12 0NN, United Kingdom; Psychopharmacology Unit, University of Bristol, Whitson Street, Bristol BS1 3NY, United Kingdom; MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Kalk
authors.affiliation: Psychopharmacology Unit, University of Bristol, Whitson Street, Bristol BS1 3NY, United Kingdom; MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Adrian
authors.initials: A
authors.lastname: Feeney
authors.affiliation: MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hammers
authors.affiliation: MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Riaño-Barros
authors.affiliation: MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Colm J
authors.initials: CJ
authors.lastname: McGinnity
authors.affiliation: Psychopharmacology Unit, University of Bristol, Whitson Street, Bristol BS1 3NY, United Kingdom.
authors.forename: Lindsay G
authors.initials: LG
authors.lastname: Taylor
authors.affiliation: MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Lula
authors.initials: L
authors.lastname: Rosso
authors.affiliation: MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom; Hammersmith Imanet Ltd., Hammersmith Hospital, Du Cane Rd., London W12 0NN, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.affiliation: MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Federico
authors.initials: F
authors.lastname: Turkheimer
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, Du Cane Rd., London W12 0NN, United Kingdom; Psychopharmacology Unit, University of Bristol, Whitson Street, Bristol BS1 3NY, United Kingdom; MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
mesh_terms: D000328:Adult; D000345:Affinity Labels / Q000493:pharmacokinetics; D000437:Alcoholism / Q000378:metabolism*; D001386:Azides / Q000493:pharmacokinetics*; D001569:Benzodiazepines / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D008568:Memory; D009714:Nucleus Accumbens / Q000378:metabolism; D009293:Opioid-Related Disorders / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D000345:Affinity Labels; D001386:Azides; D002250:Carbon Radioisotopes; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C042957:Ro 15-4513