PACAP induces increased excitability in D1- and D2-expressing nucleus accumbens medium spiny neurons

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.