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Dopaminergic cellular and circuit contributions to kappa opioid receptor mediated aversion.
Neurochem Int 2019; 129:104504NI

Abstract

Neural circuits that enable an organism to protect itself by promoting escape from immediate threat and avoidance of future injury are conceptualized to carry an "aversive" signal. One of the key molecular elements of these circuits is the kappa opioid receptor (KOR) and its endogenous peptide agonist, dynorphin. In many cases, the aversive response to an experimental manipulation can be eliminated by selective blockade of KOR function, indicating its necessity in transmitting this signal. The dopamine system, through its contributions to reinforcement learning, is also involved in processing of aversive stimuli, and KOR control of dopamine in the context of aversive behavioral states has been intensely studied. In this review, we have discussed the multiple ways in which the KORs regulate dopamine dynamics with a central focus on dopamine neurons and projections from the ventral tegmental area. At the neuronal level, KOR agonists inhibit dopamine neurons both in the somatodendritic region as well as at terminal release sites, through various signaling pathways and ion channels, and these effects are specific to different synaptic sites. While the dominant hypotheses are that aversive states are driven by decreases in dopamine and increases in dynorphin, reported exceptions to these patterns indicate these ideas require refinement. This is critical given that KOR is being considered as a target for development of new therapeutics for anxiety, depression, pain, and other psychiatric disorders.

Authors+Show Affiliations

Department of Neurology, Alcohol and Addiction Research Group, University of California, San Francisco, 675 Nelson Rising Lane, Box 0444, San Francisco, CA, 94143, USA. Electronic address: elyssa.margolis@ucsf.edu.Department of Psychology, Developmental Exposure Alcohol Research Center, Center for Developmental and Behavioral Neuroscience, Binghamton University - SUNY, 4400 Vestal Parkway East, Binghamton, NY, 13902, USA. Electronic address: akarkhan@binghamton.edu.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31301327

Citation

Margolis, Elyssa B., and Anushree N. Karkhanis. "Dopaminergic Cellular and Circuit Contributions to Kappa Opioid Receptor Mediated Aversion." Neurochemistry International, vol. 129, 2019, p. 104504.
Margolis EB, Karkhanis AN. Dopaminergic cellular and circuit contributions to kappa opioid receptor mediated aversion. Neurochem Int. 2019;129:104504.
Margolis, E. B., & Karkhanis, A. N. (2019). Dopaminergic cellular and circuit contributions to kappa opioid receptor mediated aversion. Neurochemistry International, 129, p. 104504. doi:10.1016/j.neuint.2019.104504.
Margolis EB, Karkhanis AN. Dopaminergic Cellular and Circuit Contributions to Kappa Opioid Receptor Mediated Aversion. Neurochem Int. 2019;129:104504. PubMed PMID: 31301327.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopaminergic cellular and circuit contributions to kappa opioid receptor mediated aversion. AU - Margolis,Elyssa B, AU - Karkhanis,Anushree N, Y1 - 2019/07/10/ PY - 2018/12/13/received PY - 2019/07/07/revised PY - 2019/07/10/accepted PY - 2020/10/01/pmc-release PY - 2019/7/14/pubmed PY - 2019/7/14/medline PY - 2019/7/14/entrez SP - 104504 EP - 104504 JF - Neurochemistry international JO - Neurochem. Int. VL - 129 N2 - Neural circuits that enable an organism to protect itself by promoting escape from immediate threat and avoidance of future injury are conceptualized to carry an "aversive" signal. One of the key molecular elements of these circuits is the kappa opioid receptor (KOR) and its endogenous peptide agonist, dynorphin. In many cases, the aversive response to an experimental manipulation can be eliminated by selective blockade of KOR function, indicating its necessity in transmitting this signal. The dopamine system, through its contributions to reinforcement learning, is also involved in processing of aversive stimuli, and KOR control of dopamine in the context of aversive behavioral states has been intensely studied. In this review, we have discussed the multiple ways in which the KORs regulate dopamine dynamics with a central focus on dopamine neurons and projections from the ventral tegmental area. At the neuronal level, KOR agonists inhibit dopamine neurons both in the somatodendritic region as well as at terminal release sites, through various signaling pathways and ion channels, and these effects are specific to different synaptic sites. While the dominant hypotheses are that aversive states are driven by decreases in dopamine and increases in dynorphin, reported exceptions to these patterns indicate these ideas require refinement. This is critical given that KOR is being considered as a target for development of new therapeutics for anxiety, depression, pain, and other psychiatric disorders. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/31301327/Dopaminergic_cellular_and_circuit_contributions_to_kappa_opioid_receptor_mediated_aversion L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(18)30678-8 DB - PRIME DP - Unbound Medicine ER -