Ortega-Tinoco S, Padilla-Orozco M, Hernández-Vázquez F, Garduño J, Mondragón-García A, Ramírez-Sánchez E, Bargas J, Hernández-López S
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, Mexico.
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, Mexico.
Brain Res Bull. 2025 May;224:111323. doi: 10.1016/j.brainresbull.2025.111323. Epub 2025 Mar 25.
One of the main eating disorders associated with overweight and obesity is binge eating disorder. Binge eating is characterized by excessive consumption of high-calorie foods over a short period of time, approximately 2 hours. The nucleus accumbens (NAc) plays a key role in modulating the hedonic value of high-calorie foods, commonly referred to as palatable foods. Specific subregions of the shell portion of the NAc (NAcSh), known as hedonic hot spots, may play an important role in the motivational aspect of food consumption. Previous work has shown that the pituitary adenylate cyclase-activating polypeptide (PACAP) injected into the NAc reduces palatable food intake, suggesting that this peptide could be a potential tool for treating binge eating. However, the mechanisms of action of PACAP on the NAc are poorly understood. Here, we used whole-cell recording and calcium imaging techniques in NAcSh brain slices from D1-Cre and A2A-Cre mice to investigate PACAP modulation of medium spiny neuron (MSN) activity. We found that PACAP administration increased the firing rate of D1- and D2-expressing MSNs. In addition, in a binge-eating mouse model, nasal PACAP reduced binge-eating behavior.
与超重和肥胖相关的主要饮食失调症之一是暴饮暴食症。暴饮暴食的特点是在短时间内（约2小时）过量食用高热量食物。伏隔核（NAc）在调节高热量食物（通常称为美味食物）的享乐价值方面起着关键作用。伏隔核壳部（NAcSh）的特定亚区域，即所谓的享乐热点，可能在食物消费的动机方面发挥重要作用。先前的研究表明，向伏隔核注射垂体腺苷酸环化酶激活多肽（PACAP）可减少美味食物的摄入量，这表明该肽可能是治疗暴饮暴食的潜在工具。然而，PACAP对伏隔核的作用机制尚不清楚。在这里，我们使用全细胞记录和钙成像技术，对来自D1-Cre和A2A-Cre小鼠的NAcSh脑片进行研究，以探究PACAP对中等棘状神经元（MSN）活动的调节作用。我们发现，给予PACAP可提高表达D1和D2的MSN的放电频率。此外，在暴饮暴食小鼠模型中，经鼻腔给予PACAP可减少暴饮暴食行为。
