The Role of LVV‐H7 in Alcohol‐Induced Reward Mechanisms

This study aimed to investigate the role of LVV-hemorphin-7 (LVV-H7) in alcohol dependence. LVV-H7 is a short peptide derived from the cleavage of haemoglobin chains that binds to opioid receptors and plays diverse roles in various physiological and pathological processes. Additionally, LVV-H7 is cleaved at higher concentrations in the presence of alcohol. We conducted behavioural experiments in animal models and performed proteomic analyses of CNS tissues from alcohol-addicted rats to identify LVV-H7 binding partners. Using fluorescent microscopy, we confirmed the blood-brain barrier (BBB) permeability of synthesized LVV-H7 and its releasing enzyme inhibitor, pepstatin. Our results revealed a dose-dependent correlation between LVV-H7 quantities and alcohol levels. Mass spectrometry-based analyses identified LVV-H7's protein-binding targets in CNS tissues of addicted rats and the enzymes responsible for their degradation. These findings highlight the significant role of LVV-H7 in the mechanisms underlying alcohol dependence and indicate the potential role of hemorphin as a therapeutic target.