Central amygdala neuropeptide Y neurons drive hedonic ingestive behaviour independent of energy homeostasis

BACKGROUND/OBJECTIVES: Neuropeptide Y (NPY), a key orexigenic neurotransmitter, is widely expressed in the central nervous system, including in a distinct subpopulation of neurons within the central nucleus of the amygdala (CeA). While CeA NPY neurons contribute to energy regulation during chronic stress or high-fat diet exposure, the role of these neurons in modulating ingestive behaviour under standard conditions, particularly in response to caloric and non-caloric cues remains poorly understood. SUBJECTS/METHODS: transgenic mice, enabling precise control of their activity in freely behaving animals. RESULTS: Our experiments revealed that activation of these neurons significantly increased the consumption of both caloric and non-caloric palatable solutions, without affecting overall macronutrient preference. These findings indicate that CeA NPY neurons drive reward-related ingestive behaviour, promoting excess consumption beyond homoeostatic energy needs, regardless of the nutritional value of food. Importantly, this effect was observed independently of metabolic stress or dietary manipulation, suggesting that CeA NPY neurons engage a neural pathway that prioritizes food consumption based on reward value alone. CONCLUSION: This study provides novel insights into the neurobiological mechanisms underlying reward-driven consumption and identifies CeA NPY neurons as a key node in the neural circuitry mediating hedonic appetite. These findings have potential implications for understanding the pathophysiology of overeating and for developing targeted interventions for disorders characterized by dysregulated reward-based consumption.