Neuroinflammation contributes to high salt intake-augmented neuronal activation and active coping responses to acute stress.

High dietary salt intake (HDSI) increases risk of stress-related neuropsychiatric disorders. Here, we explored the contribution of HDSI-induced neuroinflammation in key stress-responsive brain regions, the hypothalamic paraventricular nucleus (PVN) and basolateral amygdala (BLA), in promoting exaggerated neuronal activation and coping behaviors in response to acute psychogenic stress. Mice that underwent HDSI exhibited increased active stress coping behaviors during and after an acute swim stress, and these were reduced by concurrent administration of minocycline, an inhibitor of microglial activation, without affecting body fluid hyperosmolality caused by HDSI. Moreover, minocycline attenuated HDSI-induced increases of PVN TNF-α, activated microglia (Iba1), and acute swim stress-induced neuronal activation (c-Fos). In the BLA, similar effects were observed on Iba1+ and c-Fos+ counts, but not TNF-α levels. These data indicate that HDSI promotes neuroinflammation, increasing recruitment of neurons in key stress-associated brain regions and augmenting behavioral hyper-responsivity to acute psychological stress.