Insulin in the ventral tegmental area reduces hedonic feeding and suppresses dopamine concentration via increased reuptake.

Mesolimbic dopamine (DA) signaling has been implicated in the incentive, reinforcing and motivational aspects of food intake. Insulin receptors are expressed on dopaminergic neurons of the ventral tegmental area (VTA), and insulin may act in the VTA to suppress feeding. However, the neural mechanisms underlying insulin effects in the VTA are poorly understood. Here, we measured the effects of insulin on evoked DA concentration in the VTA using fast-scan cyclic voltammetry. Insulin concentration-dependently reduced evoked somatodendritic DA in the VTA, requiring activation of phosphoinositol 3-kinase and mTOR signaling. Insulin depression of somatodendritic DA was abolished in the presence of a selective DA transporter (DAT) inhibitor, GBR 12909, as well as in VTA slices of DAT knockout mice, suggesting that insulin upregulated the number or function of DAT to reduce DA concentration. Finally, insulin administered to the VTA depressed sated feeding of sweetened high-fat food. Taken together, these results indicate that insulin depresses DA concentration in the VTA via increased reuptake of DA through DAT. Insulin-mediated decrease of DA in the VTA may suppress salience of food once satiety is reached.