Dynorphin/kappa-opioid receptor control of dopamine dynamics: Implications for negative affective states and psychiatric disorders

• Published in: Brain research 2019-06, Vol.1713, p.91-101
• Main Authors: Tejeda, Hugo A., Bonci, Antonello
• Format: Article
• Language: English
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2018.09.023

•The dynorphin/kappa-opioid receptor system mediates negative affective states.•The dynorphin/kappa-opioid receptor system is enriched in dopaminergic systems.•Kappa-opioid receptor signaling in dopaminergic systems drives negative affect.•Kappa-opioid receptors inhibit dopamine neurotransmission.•Kappa-opioid receptors inhibit excitatory/inhibitory transmission in DA neurons. Negative affective states are prevalent symptoms in a plethora of neuropsychiatric disorders, including depression and drug addiction. Dysfunction of mesocorticolimbic dopamine systems has been implicated in negative affective states in neuropsychiatric disorders. The dynorphin/kappa-opioid receptor system is a powerful effector of stress-related behavior and is highly enriched within the mesocorticolimbic dopamine system. Dysfunction of dynorphin/KOR signaling within the mesocorticolimbic dopamine system is implicated in promoting symptoms in neuropsychiatric disorders. As such, the kappa-opioid receptor system provides an important therapeutic target to treat negative affective states associated with psychiatric disorders. In this review, we provide a comprehensive overview of the dynorphin/kappa-opioid receptor system and its role in regulating the mesocorticolimbic dopamine system, motivation, and emotional behavior. Furthermore, we highlight unresolved issues in the field and offer some insights for future research.