μ-opioid receptor system mediates reward processing in humans

Abstract

The endogenous μ-opioid receptor (MOR) system regulates motivational and hedonic processing. We tested directly whether individual differences in MOR are associated with neural reward responses to food pictures in humans. We scanned 33 non-obese individuals with positron emission tomography (PET) using the MOR-specific radioligand [¹¹C]carfentanil. During a functional magnetic resonance imaging (fMRI) scan, the subjects viewed pictures of appetizing versus bland foods to elicit reward responses. MOR availability was measured in key components of the reward and emotion circuits and used to predict BOLD-fMRI responses to foods. Viewing palatable versus bland foods activates regions involved in homeostatic and reward processing, such as amygdala, ventral striatum, and hypothalamus. MOR availability in the reward and emotion circuit is negatively associated with the fMRI reward responses. Variation in MOR availability may explain why some people feel an urge to eat when encountering food cues, increasing risk for weight gain and obesity.

Fig. 1

Experimental design for fMRI. Subjects viewed alternating 15.75-s epochs with palatable foods, non-palatable foods or cars. Each block contained six stimuli from one category, intermixed with fixation crosses

Fig. 2

Mean distribution of MOR in the brain as measured with [¹¹C]carfentanil (n = 33) showing widespread MOR expression with highest densities in striatum, thalamus, and cingulate cortex

Fig. 3

Association between BMI and MOR availability in the amygdala (n = 33). The full-volume data are shown at p < 0.05 uncorrected for visualization purposes

Fig. 4

BOLD responses to food pictures. Top row: Brain regions where BOLD-fMRI responses were larger when viewing palatable versus non-palatable foods (n = 33). Bottom row: brain regions where MOR availability in thalamus were negatively associated with BOLD-fMRI responses when viewing palatable versus non-palatable foods (p < 0.05, FDR corrected at cluster level). Colourbar shows the T statistic range

Fig. 5

Regional association and least-squares regression lines between BOLD-fMRI contrast to palatable minus non-palatable foods in the orbitofrontal cortex (OFC) and [¹¹C]carfentanil BP_ND in the thalamus and ventral striatum (n = 33). The data are plotted for visualization purposes only, and statistical inference is based on the full-volume analysis

Fig. 6

Cumulative map showing the number of ROIs (out of 10) whose [¹¹C]carfentanil BP_ND was correlated (p < 0.05, FDR corrected at cluster level) with the voxel-wise BOLD responses to palatable versus non-palatable foods in each brain area (n = 33)