The role of the habenula in the transition from reward to misery in substance use and mood disorders

Albert Batalla, Judith R. Homberg, Tatiana V. Lipina, Guillaume Sescousse, Maartje Luijten, Svetlana A. Ivanova, Arnt F.A. Schellekens, Anton J.M. Loonen

    Research output: Contribution to journalReview articlepeer-review

    32 Citations (Scopus)


    The habenula (Hb) is an evolutionary well-conserved structure located in the epithalamus. The Hb receives inputs from the septum, basal ganglia, hypothalamus, anterior cingulate and medial prefrontal cortex, and projects to several midbrain centers, most importantly the inhibitory rostromedial tegmental nucleus (RMTg) and the excitatory interpeduncular nucleus (IPN), which regulate the activity of midbrain monoaminergic nuclei. The Hb is postulated to play a key role in reward and aversion processing across species, including humans, and to be implicated in the different stages of transition from recreational drug intake to addiction and co-morbid mood disorders. The Hb is divided into two anatomically and functionally distinct nuclei, the lateral (LHb) and the medial (MHb), which are primarily involved in reward-seeking (LHb) and misery-fleeing (MHb) behavior by controlling the RMTg and IPN, respectively. This review provides a neuroanatomical description of the Hb, discusses preclinical and human findings regarding its role in the development of addiction and co-morbid mood disorders, and addresses future directions in this area.

    Original languageEnglish
    Pages (from-to)276-285
    Number of pages10
    JournalNeuroscience and Biobehavioral Reviews
    Publication statusPublished - 1 Sep 2017


    • fmri
    • Habenula
    • Mood disorders
    • Reward
    • Substance use disorders
    • Mood Disorders/epidemiology
    • Animals
    • Habenula/physiopathology
    • Comorbidity
    • Humans
    • Avoidance Learning/physiology
    • Substance-Related Disorders/epidemiology



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