Twelve alcohol-dependent volunteers and 12 age and gender-matched healthy controls were studied with positron emission tomography and the radiotracer [11C]carfentanil, a selective mu opioid receptor radioligand. Dependent volunteers were recruited who were otherwise healthy, were detoxified from alcohol use for at least 3 weeks prior to the study, and who were experiencing high levels of urges for alcohol. Mu opioid receptor binding measures were obtained under two conditions, elicited using previously prepared individualized scripts: (1) a neutral state, during which the volunteers were instructed to focus on an event not associated with craving for alcohol, and (2) a craving state, when the volunteers were instructed to focus on an event associated with high levels of craving for alcohol. The difference between neutral and craving scans was utilized to obtain an estimate of changes in endogenous opioid release, reflected by the changes in in vivo receptor availability between conditions. Binding estimates obtained during the neutral scan were compared with those of an age-matched control group.
Baseline mu opioid receptor binding was found reduced in alcohol-dependent volunteers in the right amygdala, a region involved in emotional processing and the encoding of emotional memory. Comparisons between neutral and craving scans revealed regional increases in mu opioid receptor availability in vivo during craving. These increases reflect reductions in baseline endogenous opioid release, and were detected in the left anterior thalamus, amygdala and subgenual anterior cingulate. The deactivation of the endogenous opiois system and mu opioid receptors in the left amygdala correlated with increases in alcohol craving scores in the left amygdala.
These findings indicate both a dysregulation of mu opioid receptor mechanisms in alcohol-dependent volunteers (reductions in binding at baseline in the right amygdala, reflecting either increased release or a downregulation of the system), as well as the involvement of this neurotransmitter system in the mediation of the experience of craving for alcohol. Reductions in the baseline level of activation of the mu opioid neurotransmitter system during craving for alcohol were detected in limbic and paralimbic regions involved in emotional regulation (left anterior cingulate, anterior thalamus and amygdala).