Effects of intravenous placebo with glucose expectation on human basal ganglia dopaminergic function

Previous positron emission tomography (PET) studies have provided evidence that the psychological expectation of certain drugs combined to the placebo administration may lead to subjectively experienced placebo effects, which, in turn, are associated with dopamine (DA) release in the brain. Our recent study indicated that blind intravenous (i.v.) glucose induces DA release in male subjects. In the present study, we examined if the mere expectation of glucose (i.v. placebo) could similarly release DA in the basal ganglia. [(11)C]raclopride PET was performed for 12 lean [mean body mass index (BMI) = 22 kg/m(2)] and 12 overweight (mean BMI = 33 kg/m(2)) healthy subjects (12 men and 12 women). Each subject was imaged twice in a counter-balanced setting, after blind i.v. placebo and after open i.v. placebo. DA D2 receptor binding potentials (BP) were estimated. The results of the present study show that i.v. placebo administration with glucose expectation induces bilateral BP reduction in the ventral striatum in the male group, suggesting DA release. The stimulus did not induce dopaminergic placebo effect in the overweight or the lean group (males and females combined). Voxel-based analysis also suggested regionally selective BP increases in the dorsal striatum in the male subjects, whereas women showed no significant changes in BPs. The results support previously reported gender differences in the DA function after a pharmacological challenge (e.g., amphetamine and glucose). Also, they suggest that the DA release in the ventral striatum mediates placebo responses in the context of glucose expectation.