Dysregulated endogenous opioid signalling and reward processing in alcohol dependence

Abstract

Alcohol dependence has been estimated to affect 5.5.% of adults in Europe and has a significant impact on an individual’s physical and mental health and also substantial costs to wider society. Current treatments for alcohol dependence, such as psychosocial interventions and pharmacotherapy, have limited success. Most individuals relapse to alcohol use within a year and this reflects a substantial unmet need. Addiction has been described as a ‘reward deficient’ state and there is evidence that the endogenous opioid system, which plays an important role in reward, is dysregulated in alcohol dependence and other addictions. This thesis aimed to characterise the endogenous opioid system in abstinent alcohol dependent participants using [11C]carfentanil, a selective mu-opioid receptor (MOR) agonist positron emission tomography (PET) radioligand, and an oral 0.5mg/kg dexamphetamine challenge to examine MOR availability and endogenous opioid release. Furthermore, the associations between reward responses, measured as financial reward anticipation during a monetary incentive delay (MID) task functional magnetic resonance imaging (fMRI) paradigm, MOR availability and endogenous opioid release in healthy controls, alcohol dependent and gambling disorder participants were also examined and compared. Abstinent alcohol dependent participants did not show any differences in MOR availability compared with healthy controls, but there was evidence of blunted dexamphetamine- induced endogenous opioid release. There were associations between MID task financial reward anticipation responses and MOR availability and dexamphetamine-induced endogenous opioid release in both alcohol dependent and gambling disorder participants. The results suggest that low endogenous opioid tone may be an important factor in alcohol dependence and other addictions. There is also evidence of a link between dysregulated endogenous opioid signalling and dysregulated reward responses in addiction. Further research is required to understand how dysregulated endogenous opioid signalling is associated with relapse risk, and which treatments might be most effective in mediating dysregulated endogenous opioid signalling and reward sensitivity.