Leptin regulates the reward value of nutrient

Abstract

We developed an assay for quantifying the reward value of nutrient and used it to analyze the effects of metabolic state and leptin. In this assay, mice chose between two sippers, one of which dispensed water and was coupled to optogenetic activation of dopaminergic (DA) neurons and the other of which dispensed natural or artificial sweeteners. This assay measured the reward value of sweeteners relative to lick-induced optogenetic activation of DA neurons. Mice preferred optogenetic stimulation of DA neurons to sucralose, but not to sucrose. However, the mice preferred sucralose plus optogenetic stimulation versus sucrose. We found that food restriction increased the value of sucrose relative to sucralose plus optogenetic stimulation, and that leptin decreased it. Our data suggest that leptin suppresses the ability of sucrose to drive taste-independent DA neuronal activation and provide new insights into the mechanism of leptin's effects on food intake.

Amylin Modulates the Mesolimbic Dopamine System to Control Energy Balance

“…In particular, phasic 'spikes' in DA release in the nucleus accumbens (NAc) evoked by aspects of food reward (Brown et al, 2011;Roitman et al, 2004) have been shown to be modulated by feeding-related hormones (Cone et al, 2014) and are sufficient for food reinforcement (Domingos et al, 2011). Given that VTA AmyR activation reduces food intake as well as the motivation to work for a palatable food (Mietlicki-Baase et al, 2013b), these data collectively support the idea that a decrease in NAc DA signaling may be involved in VTA AmyR-mediated hypophagia.…”

The role of dopamine in the pursuit of nutritional value

“…The normal preference for sucrose (110-140 mM) over sucralose (0.5 mM) was reversed by pairing sucralose consumption with optogenetic stimulation of either dopamine neurons or a subset of inputs to dopamine neurons from melanin concentrating hormone (MCH)-expressing neurons of the lateral hypothalamus [38,39]. These neurons are excited by glucose via closure of ATP-gated potassium channels providing a mechanism by which changes in blood glucose could be rapidly relayed to the mesolimbic system [40].…”

“…Stimulation of these neurons is shown to increase dopamine efflux in the striatum [39]. Importantly, while direct stimulation of dopamine neurons will generate a preference for water over sucrose [38], stimulation of MCH inputs does not generate a preference for water over sucrose [39]. Thus, the ability of MCH neurons to drive feeding and dopamine release seems dependent on a palatable taste input is required as well as neuronal activity.…”

Optogenetics in neuroscience: what we gain from studies in mammals

“…Interneurons in the NAc also take part in addiction. Witten and colleagues used ChR2 value of sucrose while leptin plays the reverse role [58] . and found that they connect to other MSNs and tonically active neurons in the dorsal striatum, while in the globus pallidus, they mainly make connections with type B/C but not type A neurons.…”