P.3.11 Increased opioid receptor binding in early abstinence from dependent opioid and alcohol use and relationship to craving

Abstract

Aims: Recent PET studies have reported increased bindingof [11C]carfentanil in early abstinence from cocainedependence that is associated with craving (Zubieta et al.1996). In this study we present data on availability of theopioid receptor using the PET tracer [11C]diprenorphinein opioid and alcohol dependent subjects in earlyabstinence compared to controls. Our hypotheses werethat in both dependent groups, opioid receptor availabilitywould be increased compared with controls and that thiswould be related to craving.Methods: We recruited ten opioid and eleven alcoholdependent patients undergoing detoxification and twentyhealthy control subjects. All completed questionnairesmeasuring clinical variables, including craving.All subjects had one [11C]diprenorphine PET scanfollowing standard protocols. Four of the alcoholdependent subjects had a repeat scan after three monthsof abstinence. The PET scans were analysed to producevolume of distribution images (VD) which are an index ofavailable receptors. We extracted VD data for whole brainand 21 pre-defined regions of interest (ROIs). Subjectswere compared with controls using paired t-tests, andclinical variables were tested for correlations with VD.Results: Global [11C]diprenorphine VD was significantlyhigher in opioid dependent subjects than controls(p = 0.019). This was also found in 15 of the 21 ROIs (t-testpl0.05 uncorrected). Alcohol dependent patients showeda trend towards an increase in global, and no significantchanges were found in the.Although the opioid dependent patients craved at ahigh level there was no association with opioid receptoravailability. However, in the alcohol dependent group,an increase in craving was significantly associated withincreased availability of opioid receptors in the striatumand whole brain.The four subjects that were rescanned showed nosignificant change in VD (paired t-test pg0.05) in wholebrain or the ROIs between the two time points. At thesecond scan their craving score was still significantlypositively correlated with VD.Conclusions: We have shown an increase in opioidreceptors in early abstinence from dependent alcohol andopioid use. Although the results in our alcohol dependentgroup did not reach significance they are consistent withanother recent study (Heinz et al. 2005).This finding is most likely due to an acute increasein receptor number in early abstinence. Previous preclinicaland clinical evidence has shown no increase duringcontinuing dependent substance use. However, on its own,this study cannot exclude a state of upregulation of opioidreceptors in chronic dependence or a trait of high opioidreceptor availability as possible causes for these findings.From the emerging evidence in cocaine, opioid andalcohol dependence, opioid receptor availability seems keyin the addictive process, particularly in early abstinence.An elevation in opioid receptor availability and its positiverelationship to craving is consistent with naltrexonersability to reduce drug seeking or craving in alcoholdependence. Treatments aimed at modulating the opioidreceptor system now have a neurobiological underpinningfor their clinical efficacy.