Insulin Surges Lap against Pleasure Center of Brain

저자：   업로드：2015-10-29  조회수：

    The rise and fall of insulin levels is connected to the rise and fall of dopamine levels in the brain, though the net effects in certain brain regions have been hard to determine. In the hypothalamus, insulin activates insulin receptors, favoring dopamine reuptake and signaling satiety after a meal. In the striatal region, however, insulin’s effects are less clear. Since the striatal region is the brain’s reward and pleasure center, insulin’s effects here could influence food choices, with implications for obesity and the progress of diabetes.

    Previous attempts to determine the role of insulin in the brain’s pleasure center have yielded conflicting results. In an attempt to resolve the issue, researchers at NYU’s Langone Medical Center led by neuroscientist Margaret Rice, Ph.D., conducted laboratory and behavioral studies with rodents. These studies not only reaffirmed that insulin helps trigger the reuptake of dopamine when insulin levels rise, but also revealed that the net effect is a rise in dopamine levels. The results may also be the first to demonstrate that insulin's role in the dopamine pathway may affect and explain food choices.

    The results appeared October 27 in Nature Communications, in an article entitled, “Insulin enhances striatal dopamine release by activating cholinergic interneurons and thereby signals reward.” The article described how the investigators evaluated axonal dopamine release and uptake in the intact microenvironment of the nucleus accumbens and caudate–putamen in ex vivo striatal slices using fast-scan cyclic voltammetry (FCV), and determined the effects of insulin signaling in the nucleus accumbens on reward behavior in vivo.

    In one set of experiments, Dr. Rice and her colleagues recorded a 20–55% increase in dopamine released in the striatal region of the rodent brain (where dopamine's effects on the brain are felt and which governs the body's response to getting a reward). The rise occurred along the same timeframe as the rise in insulin activity needed to process any food sugars the mice and rats ate. And this occurred despite the reabsorption, or reuptake, of dopamine that in other regions of the brain tells an animal that its appetite is satisfied.

    Dr. Rice and study co-principal investigator Kenneth Carr, Ph.D., also conducted separate experiments with rats in which they found that animals fed low-calorie diets had a 10-fold greater sensitivity to increasing insulin levels in the brain (meaning that it took only a tenth of a rise in insulin levels as seen in rats on a normal diet to spur dopamine release). By contrast, rats on high-calorie diets lost all striatal-brain insulin responsiveness. In addition, rats offered a choice between a drink reward that was paired with either an insulin antibody injection to block hormone signaling or a mock placebo injection always favored the drink-injection combination that led to intact insulin signaling (and more dopamine).

    "Our work establishes what we believe is a new role for insulin as part of the brain's reward system and suggests that ro

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