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 18Ffallypride 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.
To elucidate the "atypicality" of ziprasidone, its striatal and extrastriatal D2/D3-receptor binding was characterized in patients with schizophrenia under steady-state conditions. These data were ...compared with striatal receptor occupancy values after single-dose ziprasidone ingestion in healthy controls. Ffallypride positron emission tomography (PET) recordings were obtained in 15 patients under steady-state ziprasidone treatment at varying time points after the last dose. Binding potentials were calculated for striatal and extrastriatal regions. D2/D3-receptor occupancies were expressed relative to binding potentials in 8 unmedicated patients. In a parallel Craclopride-PET study, striatal D2/D3-receptor occupancy was measured in healthy subjects after single oral doses of 40 mg ziprasidone or 7.5 mg haloperidol. Ziprasidone plasma concentrations correlated significantly with D2/D3-receptor occupancies in all volumes of interests. Occupancy in extrastriatal regions was approximately 10% higher than in striatal regions. Half maximal effective concentration values were consistently higher in striatal than in extrastriatal regions (temporal cortex: 39 ng/mL; putamen: 64 ng/mL), irrespective of the time between last dosing and scan. Single ziprasidone doses resulted in higher occupancies exceeding the 95% prediction limits of the occupancy versus plasma concentrations for chronic dosing. Ziprasidone shares moderate preferential extrastriatal D2/D3-receptor binding with some other atypicals. D2/D3-receptor occupancy is rapidly attuning to the daily course of ziprasidone plasma levels, suggesting relatively high intraday variations of D2/D3-receptor binding. The discrepancies between single-dose and steady-state results are important for the future design of dose-finding PET occupancy studies of novel antipsychotics. Single-dose studies may not be totally relied on for final dose selection.
Patients suffering from alcohol addiction are known to be more sensitive to painful stimulation than healthy controls. Dopamine is suggested to play a key role in pain regulation. Aim of the present ...study was to examine the relationship between brain dopamine and somatosensory perception in alcoholics and healthy controls. Temperature and touch perception were evaluated in 12 male detoxified alcohol dependent patients and 12 age matched controls using a standardized somatosensory test battery (Quantitative Sensorische Testung, QST, by Treede 2006). The AUDIT score (Alcohol Use Disorder Identification Test) was taken as means for alcohol consumption in patients (at time of drinking) and controls. Ten of the patients and 10 of the controls also underwent Positron Emission Tomography (PET) with F18fallypride to quantify D2/3 receptor availability in the brain. Binding potentials were calculated by means of the simplified reference tissue model. Sensitivity to pain negatively correlated with the AUDIT score in both, patients and controls. Moreover, a positive correlation was found between individual threshold for pressure pain and D2/3 receptor availability in the thalamus and the striatum. The results indicate a direct relationship between alcohol consumption and pain perception. They further support dopamine as mediator of pain regulation.
