High-fat diet intake induces neuroinflammation and alters the dopaminergic system in the amygdala of juvenile rats.

High-fat diet (HFD) intake is increasingly common during adolescence and is associated with neuroinflammation and amygdala-dependent behavioral alterations. Because the amygdala continues to mature throughout adolescence, this period represents a window of vulnerability to dietary and inflammatory challenges. In addition to its role in stress responses, the amygdala contributes to appetitive behaviors and receives monoaminergic inputs modulating feeding-related processes. Although HFD-induced amygdalar neuroinflammation may alter these functions, how its effects differ across developmental stages remains poorly understood. We compared the effects of 4-week HFD exposure in juvenile and adult rats (jHFD and aHFD). Both groups exhibited moderate hyperphagia. In juveniles, HFD decreased circulating corticosterone and glucocorticoid-receptor immunoreactivity in basolateral amygdala (BLA), which may reduce glucocorticoid-mediated regulation of inflammation and contribute to heightened neuroinflammatory response. Accordingly, jHFD rats showed elevated circulating IL-1β, increased amygdalar proinflammatory cytokine levels, and increased Iba-1-positive myeloid reactivity in BLA. Moreover, jHFD rats displayed reduced dopamine turnover and increased D2R immunoreactivity in BLA. In adults, HFD was associated with glial morphological alterations without the molecular profile of active neuroinflammation observed in juveniles. Thus, juvenile rats exhibited greater susceptibility to HFD-induced alterations in amygdalar neuroinflammatory and dopaminergic signaling. Despite these neurobiological differences, both age groups developed comparable hyperphagia, suggesting that these amygdalar alterations may not be sufficient to account for increased food intake under these conditions. These findings highlight the neuroimmune vulnerability associated with HFD exposure during development and reveal age-dependent effects of HFD on amygdalar function during adolescence, a period of heightened vulnerability to emotional related disorders.