Sensitivity of dopamine systems to opioidergic stimulation in alcoholism: a PET study with [18F]fallypride

It is widely accepted that the mesolimbic dopamine (DA) system plays a major role in the rewarding effects of alcohol consumption. In addition there is increasing evidence that alcohol interferes with endogenous opioid mechanisms which in return modulate dopaminergic transmission in the mesolimbic pathway. It is assumed that alcohol has (acute and chronic) effects on the binding properties of opioid receptors. Opioid agonists with affinity for µ opioid receptors are expected to develop their rewarding effect by activation of the mesolimbic dopamine system which ascends from the ventral tegmentum to the nucleus accumbens. The aim of the present study was to test for differences in sensitivity of DA reward systems to opioidergic stimulation in alcohol-dependent patients and healthy controls. D2-like DA receptors were quantified with PET and [18F]fallypride as the radiotracer in 8 male detoxified alcohol dependent patients and 8 age matched controls. Subjects underwent dynamic PET scans over 180 minutes. To test for a group difference in DA release between baseline and experimental condition, participants were scanned twice, the second time after application of the short-acting µ-opiate agonist remifentanil. Binding potentials (BP) were calculated by means of the simplified reference tissue model. DA release was calculated as percent change in BP. Craving was assessed in both conditions. The results will be presented and discussed in the light of current models of addiction.