Abstract
Interest in the habenula has greatly increased in recent years. The habenula is a small brain structure located posterior to the thalamus and adjacent to the third ventricle. Despite its small size, the habenula can be divided into medial habenula (MHb) and lateral habenula (LHb) nuclei that are anatomically and transcriptionally distinct. The habenula receives inputs from the limbic system and basal ganglia primarily via the stria medullaris. The fasciculus retroflexus is the primary habenular output from the habenula to the midbrain and governs release of glutamate onto gabaergic cells in the rostromedial tegmental nucleus (RMTg) and onto the interpeduncular nucleus. The resulting GABA released from RMTg neurons inactivates dopaminergic cells in the ventral tegmental area/substantia nigra compacta. Through this process, the habenula controls dopamine levels in the striatum. Thus, the habenula plays a critical role in reward and reward-associated learning. The LHb also modulates serotonin levels and norepinephrine release, while the MHb modulates acetylcholine. The habenula is a critical crossroad that influences the brain’s response to pain, stress, anxiety, sleep, and reward. Dysfunction of the habenula has been linked to depression, schizophrenia, and the effects of drugs of abuse. This review focuses on the possible relationships between the habenula and drug abuse.
Highlights
Reviewed by: Ines Ibañez-Tallon, Max-Delbrück-Center for Molecular Medicine, Germany Thomas Jhou, Medical University of South Carolina, USA
Much of the work linking the habenula to drug addiction is based on studies of nicotine and nicotinic receptors in the medial habenula (MHb)
Nicotine causes degeneration of the internal component of the fasciculus retroflexus, which connects the MHb to the interpeduncular nucleus (IPN)
Summary
Reviewed by: Ines Ibañez-Tallon, Max-Delbrück-Center for Molecular Medicine, Germany Thomas Jhou, Medical University of South Carolina, USA. If the reward state is positive, Abbreviations: IPN, interpeduncular nucleus; VTA, ventral tegmental area; RMTg, rostromedial tegmental nucleus; nAChR, nicotinic acetylcholine receptor; GWAS, genome-wide association study; SNP, single nucleotide polymorphism; fMRI, functional magnetic resonance imaging; SNc, substantia nigra compacta. Due to the small size of the habenula, the difficulty of doing non-invasive studies in humans, the lack of a clearly defined functional role (links to feeding behavior, pain sensitivity, anxiety, parental behavior, nicotine effects, and other behaviors were all demonstrated), and the lack of suitable pharmacological agents for habenula research, interest in the habenula began to taper off until 2007 when Matsumoto and Hikosaka published a seminal report on the habenula as a region associated with the signaling of negative prediction error events in the brain (Matsumoto and Hikosaka, 2007). The habenula was linked to addiction through a series of rodent experiments and human genome-wide association studies
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