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

Abstract

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.

Dopamine D2 Receptor Genotype (C957T) and Habitual Consumption of Sugars in a Free-Living Population of Men and Women

“…We detected a significant interaction between DRD2 genotype and sex, and therefore, stratified all our analyses to examine men and women separately. Our results are consistent with imaging studies that demonstrate differences in dopaminergic activation between men and women [4,12,13] . When men and women had been examined at baseline there was no difference in brain dopaminergic activity [4,13] .…”

“…When men and women had been examined at baseline there was no difference in brain dopaminergic activity [4,13] . However, men and women differed in their dopaminergic responses to various stimuli conditions such as expectation of glucose versus no expectation of glucose infusion, glucose infusion versus intravenous saline, and cognitive inhibition during food stimulation versus food stimulation alone [4,12,13] . Therefore, although men and women may not differ basally, they might differ throughout various aspects of the ingestive behavior process.…”

“…The relationship, however, between dopamine signaling and food reward is complex [6][7][8] , which may be explained by a non-linear inverted U-shaped dose-response curve between dopamine signaling and food intake [6,[9][10][11] . Recently, a number of studies have demonstrated different effects of dopaminergic activation across men and wom-en in response to glucose infusions, glucose expectation, and cognitive inhibitory control of hunger during food stimulation [4,12,13] , suggesting that there may be differences in food intake behaviors between men and women.…”

“…The small sample sizes of previous studies, however, may have limited the analysis in two ways [14][15][16][17][18]22] . First, men and women have not been examined separately to determine if they respond differently [4,12,13] . Second, is the use of a dominant mode of inheritance model for comparing genotypes, where individuals homozygous for the C allele were compared to carriers of the T allele.…”

The Anatomy of the Mesolimbic Reward System: A Link between Personality and the Placebo Analgesic Response

“…To test this association directly, positron emission tomography studies of dopamine binding potential and pharmacological studies that enhance or impair dopaminergic neurotransmission are needed. Thirdly, our interpretation might only apply to male subjects, since the dopaminergic system differs between genders, also with respect to expectation-induced dopamine release (Haltia et al, 2008). Last, the ventral striatum has also been implicated in the processing of aversive events, including pain (Becerra et al, 2001).…”