Activation of D2-Expressing Medium Spiny Neurons in the Nucleus Accumbens Core Mirrors the Delaying Effect of Novelty Exposure on Feeding Onset in Rats.

The nucleus accumbens core (NAcc) plays a central role in integrating reward, motivation, and environmental cues to guide goal-directed behaviors, including feeding. Within the NAcc, D2-expressing medium spiny neurons (D2-MSNs) are implicated in inhibitory control and aversive processing, yet their role in feeding initiation remains poorly understood. Using a chemogenetic approach (DREADDs) in male rats housed in calorimetry-metabolic cages, we investigated the contribution of NAcc D2-MSNs to meal patterning and locomotor activity. Activation of D2-MSNs delayed feeding onset and reduced locomotor activity, without affecting further meal patterns. Inhibition of the D2-MSNs alone had no significant effect. Notably, exposure to a novel environment produced a comparable delay in feeding initiation, which was normalized by D2-MSN inhibition in the same context. These findings suggest that NAcc D2-MSNs are recruited under conditions of environmental novelty to modulate feeding-related decision-making. Dysregulation of this system may impair behavioral flexibility and contribute to maladaptive feeding patterns, with implications for the neurobiology of eating disorders.