The research team led by Prof. Hailan Hu has recently published an article titled Stress Relief as a Natural Resilience Mechanism against Depression-like Behaviors on Neuron online on Sep 29^th, 2023. This research discovered relief as a natural resilience mechanism against depression, and deconstructed the neural circuit mechanisms underlying relief.

Unraveling relief as a homeostatic defense mechanism for mood regulation and clarifying the underlying neural circuit mechanism

Relief, the appetitive state after the termination of aversive stimuli, is evolutionarily conserved. The inherent opponency in the valence between stress and relief raises the intriguing possibility that relief may counteract the detrimental effects of stress, playing a role in stress resilience. However, such a possibility has not been tested experimentally. Understanding the behavioral role of this well-conserved phenomenon and its underlying neurobiological mechanisms are open and important questions.

Based on the correlative discovery that relief magnitude strongly correlates with resilience level to depression, researchers further revealed that blocking stress relief causes vulnerability to depression-like behaviors, whereas natural rewards supplied shortly after stress promotes resilience. Stress relief is mediated by reward-related mesolimbic dopamine neurons, which show minute-long, persistent activation after stress termination. Circuitry-wise, activation or inhibition of circuits downstream of the ventral tegmental area during the transient relief period bi-directionally regulates depression resilience. These results reveal an evolutionary function of stress relief in depression resilience, and identify the neural substrate mediating this effect. Importantly, our data suggest a behavioral strategy of augmenting positive valence of stress relief with natural rewards to prevent depression.

Website: https://www.cell.com/neuron/fulltext/S0896-6273(23)00668-2

Figure. Physiological utility of relief and underlying dopaminergic circuit mechanisms