628. DOPAMINERGIC CONTROL OF COMPULSIVE EATING

Abstract Background Compulsive eating behavior, characterized by the excessive intake of palatable high-sugar and high-fat foods despite negative consequences, may be associated with dysfunctional dopamine system, specifically involving the dopamine D2 receptor. Aims & Objectives This study aims to investigate the role of dopamine D2 receptor-expressing neurons in compulsive eating behavior, focusing on their function within the central nucleus of the amygdala (CeA). Method We selectively deleted or manipulated dopamine D2 receptor-expressing neurons in the CeA using transgenic mice and Cre-loxP system strategies. A combination of pharmacological methods, fiber photometry, optogenetics, and immunohistochemistry was employed to investigate D2R signaling in the CeA and its role in controlling compulsive eating behavior. Compulsive eating was analyzed using a palatable food (PF) self-acquisition test and a light/dark box test. Results Selective deletion of D2R in the CeA led to a significant increase in active lever pressing during the PF self-acquisition test, suggesting that CeA D2R is a crucial modulator of compulsive eating. Optogenetic and fiberphotometric analyses revealed that a decrease in CeA D2R-expressing neuronal activity is associated with PF consumption, whereas stimulation of CeA D2R-expressing neuronal activity attenuates compulsive eating. These findings suggest that D2R signaling in the CeA plays a crucial role in regulating reward-driven and compulsive eating behaviors. Discussion & Conclusions Our findings demonstrate that dopamine D2 receptor (D2R) signaling in the central nucleus of the amygdala (CeA) is a key regulator of compulsive eating. The increased compulsive food-seeking behavior in CeA-D2R knockout mice, along with optogenetic evidence, suggests that impaired D2R function contributes to maladaptive food consumption patterns, linking CeA dopamine dysfunction to compulsive eating. These studies may provide a basis for developing new approaches to managing neuropsychiatric and metabolic disorders associated with maladaptive eating behaviors. [This work was supported by the Bio & Medical Technology Development Program (Grant#: 2016M3A9D5A01952412 and RS-2024-00398223) and Mid-Career Researcher Program (Grant#: 2020R1A2C2101010) from the National Research Foundation of Korea (NRF) by the Ministry of Science, ICT & Future Planning.]