HCRTR1 and major depressive disorder: By establishing a variety of in vivo models, including the CUMS model, and directly intervening in hypocretin‐1 or establishing models of HCRTR1 knockdown in the hippocampus, we further explored the specific mechanism of hypocretin‐1 involvement in depression, Our data suggest that hypocretin‐1 regulates the glycolytic pathway, and that HCRTR1 affects the reduction of lactate release from hippocampal astrocytes and impairs synaptic plasticity and neurogenesis, thus playing an important role in depressive cognitive dysfunction.