Central insulin modulates dopamine signaling in the human striatum.

Abstract

OBJECTIVE\nActivity in the dopaminergic pathways of the brain is highly sensitive to body weight and metabolic states. Animal studies show that dopamine neurons are important targets for the metabolic hormone insulin with abolished effects in the insulin resistant state, leading to increases in body weight and food intake. In humans, the influence of central acting insulin on dopamine and effects of their interplay are still elusive.\n\n\nRESEARCH DESIGN AND METHODS\nWe investigated whether central administered insulin influences dopaminergic activity in striatal regions and whole-brain neural activity. Using a PET/MRI hybrid scanner, we simultaneously performed [ 11C]-raclopride-PET and resting state fMRI in 10 healthy normal weight men after application of intranasal insulin or placebo on two separate days in a randomized, placebo-controlled, blinded, crossover trial.\n\n\nRESULTS\nIn response to central insulin compared to placebo administration, we observed greater [ 11C]-raclopride binding potential (BPnd) in the bilateral ventral and dorsal striatum. This suggests an insulin-induced reduction in synaptic dopamine levels. Resting-state striatal activity was lower 15 and 30\xa0min after nasal insulin compared to placebo. Functional connectivity of the mesocorticolimbic circuitry associated with differences in dopamine levels: individuals with a stronger insulin-induced effect on dopamine levels showed a stronger increase in functional connectivity 45\xa0min after intranasal insulin.\n\n\nCONCLUSIONS\nThis study indicates that central insulin modulates dopaminergic tone in the striatum, which may affect regional brain activity and connectivity. Our results deepen the understanding of the insulin-dopamine interaction and the complex network that underlies the regulation of whole-body metabolism.