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 and lateral 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 to the midbrain.

This fasciculus retroflexus output from the lateral habenula governs the release of glutamate onto gabaergic cells in the rostromedial tegmental nucleus. The resulting GABAergic release 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 lateral habenula also modulates serotonin levels and norepinephrine release, while the medial habenula modulates acetylcholine.

The habenula is a critical crossroads that influences the brain’s response to pain, stress, anxiety, sleep, and reward. Dysfunction of the habenula has been linked to depression, schizophrenia, and drug addiction. This review is focused on the possible relationship between the habenula and drug addiction.

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