Hcrtr1, also known as OX1R, is a G-protein-coupled receptor. The endogenous ligands for Hcrtr1 are hypocretin/orexin neuropeptides. Hcrtr1 is associated with the regulation of motivation, reward, and autonomic functions, and is involved in the sleep-wake regulatory circuitry [1].

Hcrtr1 null mice displayed a significant reduction in behavioral despair in the forced swim test and tail suspension test, suggesting that Hcrtr1 signaling may have a role in modulating depression-like behaviors [4]. Also, a high-fat diet may induce depression-like phenotypes via hypocretin-Hcrtr1 mediated inflammation activation, and the Hcrtr1 antagonist SB334867 could reverse some adverse effects [3]. Moreover, an Hcrtr1 gene variant (rs2271933 G > A) has been associated with aggressive behavior, with Hcrtr1 A/A homozygotes showing higher aggression, and this genotype effect was dependent on the experience of stressful life events [2].

In conclusion, Hcrtr1 is crucial for functions related to motivation, reward, and autonomic activities. Research using Hcrtr1 knockout mouse models has revealed its significance in depression-like behaviors and aggressive behavior. Understanding Hcrtr1 may provide insights into the mechanisms of related mental disorders and potentially lead to new treatment strategies.