Acute stress suppresses hunger-driven food seeking through PVN activation: Reversal by anxiolytic drug and ghrelin receptor agonist, with anxiolytic-like effects of refeeding.

This mouse study examined how acute restraint stress (30 minutes) interferes with hunger-driven food-seeking behavior and what interventions can reverse this effect. Using a conflict-based open-field feeding paradigm, researchers found that restraint stress abolished the increases in food seeking and intake normally observed in fasted mice. Two pharmacological interventions — intraperitoneal diazepam (an anxiolytic) and MK-677 (a ghrelin receptor agonist) — both reversed this stress-induced suppression of feeding behavior, though through apparently distinct neural mechanisms. To map neural correlates, the study measured c-Fos (a marker of neuronal activation) and phosphorylated pyruvate dehydrogenase (pPDH, a marker of neuronal inhibition) in the paraventricular hypothalamic nucleus (PVN). Diazepam reduced restraint-induced c-Fos expression in the PVN, suggesting anxiolysis works via suppressing stress-driven PVN activation, while MK-677 increased pPDH, indicating a separate feeding-drive mechanism. Notably, refeeding after fasting produced a pPDH-dominant PVN pattern and also reduced anxiety-related behaviors, suggesting physiological restoration of energy balance may itself confer stress resilience. Key limitations include exclusive use of a mouse model, the use of a single stress paradigm, and the lack of direct causal circuit manipulations. Findings are not directly applicable to humans without further study.

Why this grade: All experiments were conducted exclusively in mice using a restraint stress and open-field paradigm, with no human subjects or clinical data involved.