A Role for the Lateral Habenula in Heroin Withdrawal

Post-Traumatic Stress Disorder is a damaging mental disorder that is increasing in prevalence in America. While PTSD has been studied for decades, very little is still understood about its development and maintenance. Additionally, another issue plaguing the country is the ongoing opioid crisis, marked by high levels of opioid use and overdose death. One of the key factors driving these rates is the impact and damage done by opioid withdrawal. Individuals with Opioid Use Disorder often report a wide range of severe symptoms associated with withdrawal from drugs like heroin, indicating these as a driving force behind relapse and continued use. Given the comorbidity of the two disorders, developing an understanding of how they function together and how their mechanisms work with one another could provide novel insight into potential avenues for treating both conditions. While previous research has suggested a role for the Dorsal Hippocampus, a region involved in memory formation and spatial navigation, implicating a functional role for the hippocampus in heroin withdrawal, the complex nature and interconnectivity of the brain suggests that this isn’t the only region involved in these processes, raising the question of the involvement of other regions. Another potential region of interest in heroin withdrawal is the Lateral Habenula. The Lateral Habenula is brain region involved in the processing of aversive stimuli and negative emotional affect. It has been functionally implicated in different models of Major Depressive Disorder and withdrawal from other substances of abuse. Given this information, the research looking into the role of the LHb in heroin use and withdrawal is very sparse.The present dissertation aimed to assess if the LHb is influenced by heroin withdrawal, and also to assess if the region is functionally relevant to mechanisms and outcomes of heroin withdrawal. The first aim served to identify if heroin withdrawal influences activity in the LHb, while the second aim of this dissertation aimed to assess the functional relevance of these changes in LHb activity. The results of this dissertation reveal a potential role for LHb neurons in heroin withdrawal, while also providing several avenues for future study.