Consumption of palatable food primes food approach behavior by rapidly increasing synaptic density in the VTA

In an environment with easy access to highly palatable and energy-dense food, food-related cues drive food-seeking regardless of satiety, an effect that can lead to obesity. The ventral tegmental area (VTA) and its mesolimbic projections are critical structures involved in the learning of environmental cues used to predict motivationally relevant outcomes. Priming effects of food-related advertising and consumption of palatable food can drive food intake. However, the mechanism by which this effect occurs, and whether these priming effects last days after consumption, is unknown. Here, we demonstrate that short-term consumption of palatable food can prime future food approach behaviors and food intake. This effect is mediated by the strengthening of excitatory synaptic transmission onto dopamine neurons that is initially offset by a transient increase in endocannabinoid tone, but lasts days after an initial 24-h exposure to sweetened high-fat food (SHF). This enhanced synaptic strength is mediated by a long-lasting increase in excitatory synaptic density onto VTA dopamine neurons. Administration of insulin into the VTA, which suppresses excitatory synaptic transmission onto dopamine neurons, can abolish food approach behaviors and food intake observed days after 24-h access to SHF. These results suggest that even a short-term exposure to palatable foods can drive future feeding behavior by rewiring mesolimbic dopamine neurons.