Role of Lateral Hypothalamic Orexin (Hypocretin) Neurons in Alcohol Use and Abuse: Recent Advances

Abstract

Alcohol use disorders (AUDs) are chronic relapsing disorders with the modest efficacy of current medications. The US Food and Drug Administration (FDA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) approval of the dual orexin (OX) receptor antagonist, suvorexant for the treatment of insomnia, may enable repurposing of this drug for the treatment of other diseases. Here, we summarize and reflect on the most recent research on the role of OX neurons in alcohol use and abuse. OX neurons regulate alcohol intake and seeking, although their involvement in different aspects of alcohol consumption/seeking, specific loci of action and interactions with other transmitter systems are still being clarified. Recent studies have identified anatomic loci of action and interactions between OX and other neuropeptides that drive alcohol seeking. Future studies are required to fully elucidate these behaviors, in which optogenetic and chemogenetic approaches may prove useful.