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

Abstract

In an environment with easy access to highly palatable and energydense 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.palatable food | synaptic density | VTA | dopamine | excitatory synaptic transmission P riming effects of food-related advertising (1) and consumption of palatable food (2, 3) can drive sated consumption of food. Overconsumption of food relative to need is an important factor in the development of obesity (4). The priming effects of palatable food on food intake are likely a considerable factor in the obesity epidemic. However, the mechanism by which food-priming effects occur is unknown. The ventral tegmental area (VTA) and its mesolimbic projections are critical for learning about environmental cues used to predict motivationally relevant outcomes (5). Indeed, food-related cues activate the dopaminergic circuit to reinforce food intake (6, 7). VTA dopamine neurons can increase or decrease their synaptic efficacy to modulate their consequent dopaminergic output (8, 9). The strength of excitatory synaptic input onto VTA dopamine neurons plays a central role in rewardrelated behavior with potentiation of synapses formed onto VTA neurons, facilitating the transformation of neutral environmental stimuli into salient reward predictive cues (8). Conversely, depression of excitatory synaptic transmission would likely reduce the intrinsic firing rate and excitability of dopamine neurons, as has been demonstrated for other neurons (10), and would likely reduces the salience of reward predicting cues.The motivation to eat is regulated by a variety of intrinsic and extrinsic factors. Metabolic signals, including neuronal or circulating peptides released in response to internal states such as hunger ...

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