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

Year: 2025
Type: article
Abstract: Feeding behavior is influenced by both metabolic drive and emotional context, yet how acute stress interferes with hunger-driven motivation remains poorly understood. Using a conflict-based open-field feeding paradigm, we examined how 30-min restraint stress alters food-seeking behavior in fasted mice and how pharmacological or physiological interventions modulate this effect. Acute restraint abolished fasting-induced increases in food seeking and intake, an effect that was reversed by intraperitoneal diazepam, an anxiolytic, and by MK-677, a ghrelin receptor agonist that enhances appetite. To identify neural correlates, we quantified c-Fos (neuronal activation) and phosphorylated pyruvate dehydrogenase (pPDH; neuronal inhibition) in the paraventricular hypothalamic nucleus (PVN). Diazepam suppressed restraint-induced c-Fos expression, whereas MK-677 increased pPDH, revealing distinct PVN signatures for anxiolysis and enhanced feeding drive. Notably, refeeding after fasting induced a similar pPDH-dominant pattern and attenuated stress-induced anxiety-related behaviors, indicating that restoration of energy balance exerts intrinsic anti-stress effects through PVN inhibition. Together, these findings reveal that acute stress suppresses hunger-driven food seeking via PVN activation, pharmacological inhibition reverses this suppression, and physiological refeeding promotes stress resilience via PVN-medicated inhibition, highlighting PVN modulation as a shared mechanism linking emotional and metabolic homeostasis.
DOI: 10.1016/j.neures.2025.104989
Authors: Ryusei Tojo, Mayuka Tashiro, Haruka Takahashi, Hideki Tamura
Institution: Hoshi University
Language: English
Open Access status: gold
Estimated APC paid: $2,770
OpenAlex ID: W4416410573
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Cites: 37
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