Neural circuits for stress-induced water drinking in relief of anxiety

Drinking water is a rapid, instinctive behavior of mammals following stress. The role of such stress-induced water drinking behavior and its neural mechanisms remain poorly known. Here, we identify two sequentially activated neural circuits that respectively mediate stress-induced drinking behavior and reward encoding, which collectively promote the extinction of anxiety-like behaviors in mice. Specifically, mild short-term stress induces anxiety-like behaviors and activates glutamatergic neurons in the medial prefrontal cortex (mPFC^Glu) projecting to glutamatergic neurons in the median preoptic nucleus (MnPO^Glu), consequently driving drinking behavior in mice. This drinking behavior subsequently activates GABAergic neurons in the MnPO (MnPO^GABA), which then inhibit GABAergic neurons in the ventral tegmental area (VTA^GABA), leading to disinhibition of reward-encoding dopaminergic VTA neurons (VTA^DA), ultimately mediating the extinction of stress-induced anxiety-like behaviors. The present study defines cortical-hypothalamic-midbrain connections underlying the anxiety-relieving effects of drinking behavior, providing a circuit basis for innate stress coping strategies.