The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in
addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [ 23 11C]Ro15 4513, we previously showed reduced
binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that 24
reduced [ 25 11C]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 26
further we assessed [ 27 11C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis
to estimate contributions of α1 and α5 subtypes to [ 28 11C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent
groups. Opiate substitute maintained opiate-dependent men (n = 12) underwent an [ 29 11C]Ro15
4513 PET scan and compared with matched healthy controls (n = 13). We found a significant reduction in 30
[ 31 11C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control
group. There was no relationship between [ 32 11C]Ro15 4513 binding in the hippocampus with memory. We
found that reduced [ 33 11C]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 34
performance and [ 35 11C]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 depen- 36
dence to two pharmacologically different substances, alcohol and opiates.