Many of our daily behaviors and social interactions revolve around seeking and obtaining food. While adaptive ingestive behaviors not only support our physical health, consuming our favorite meals has the added benefit of being highly enjoyable, and ensures that we will devote our attention to obtaining preferred foods in the future. Feeding behaviors are highly complex as they not only rely on a distributed network of neurons to orchestrate these important processes, but they also require satiety signaling hormones from the periphery which act within the brain on discrete populations of cells to regulate neuronal activity that initiates and controls food intake (Figlewicz & Sipols, 2010). These neuronal circuits, many of which are composed of neurons within limbic brain regions such as the hypothalamus, nucleus accumbens and ventral tegmental area, act in concert to promote and reinforce food seeking (Kenny, 2011). Furthermore, understanding how satiety signals alter neuronal function is of high clinical importance given the growing obesity epidemic throughout the world (James et al., 2001).
In this issue of EJN, Mebel and colleagues demonstrate that one critical satiety signal, insulin, directly suppresses ventral tegmental area (VTA) dopamine neurotransmission – a key component in reward processing. Insulin, which is released from the pancreas in response to food intake, enters the bloodstream and through active transport reaches the brain (Woods et al., 2003). VTA dopamine neurons express insulin receptors (Figlewicz et al., 2003) that may act to regulate dopamine neuronal activity and subsequent release, although functional data linking insulin signaling in the VTA to alterations in neurotransmission have been lacking. In the current study, the authors used fast-scan cyclic voltammetry to monitor somato-dendritic dopamine release from VTA neurons in response to exogenous insulin in live brain slices. Insulin dose-dependently reduced evoked dopamine release, which was dependent on phosphoinositol 3-kinase and mammalian target of rapamycin (mTOR) signaling pathways. Importantly, when these experiments where conducted in mice lacking the dopamine transporter (DAT) or in the presence of a DAT inhibitor, insulin failed to reduce dopamine release, suggesting that insulin-mediated signaling may increase the expression or activity of DAT, which would lead to enhanced clearance of released dopamine. To complement the slice physiology experiments and to provide validity of this mechanism of insulin to suppress dopamine signaling, the authors also demonstrated that intra-VTA insulin administration could reduce food intake of a palatable high-fat food in sated animals. These data provide a compelling mechanism by which satiety signaling hormones such as insulin can regulate brain reward circuitry. By directly regulating the activity of neuronal circuits involved in reward processing, satiety-signaling hormones are probably providing important feedback to regulate motivated behaviors directed at obtaining food. Given the high costs that eating disorders and obesity exact on society, further investigation of the neural mechanism by which satiety signals can regulate reward-related behaviors is of critical importance.