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KOR Control over Addiction Processing: An Exploration of the Mesolimbic Dopamine Pathway

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Image The Kappa Opioid Receptor

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 271))

Abstract

Drug addiction is a complex, persistent, and chronically relapsing neurological disorder exacerbated by acute and chronic stress. It is well known that the dynorphin/kappa opioid receptor (KOR) system regulates stress perception and responsivity, while the mesolimbic dopamine system plays a role in reward and reinforcement associated with alcohol and substance use disorders. Interestingly, the dopamine and dynorphin/KOR systems are highly integrated in mesolimbic areas, with KOR activation leading to inhibition of dopamine release, further altering the perception of reinforcing and aversive stimuli. Chronic or repeated exposure to stress or drugs potentiates KOR function ultimately contributing to a hypodopaminergic state. This hypodopaminergic state is one of the hallmarks of hyperkatifeia, defined as the hypersensitivity to emotional distress that is exacerbated during drug withdrawal and abstinence. The relationship between stress and drug addiction is bidirectional; repeated/chronic stress promotes pro-addictive behaviors, and repeated cycles of drug exposure and withdrawal, across various drug classes, produces stress. Neuroadaptations driven by this bidirectional relationship ultimately influence the perception of the reinforcing value of rewarding stimuli. In this chapter, we address the involvement of the dopamine and dynorphin/KOR systems and their interactions in shaping reinforcement value processing after drug and stress exposure, as well as a combinatorial impact of both drugs and stress.

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  1. Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Paige M. Estave

  2. Department of Psychology, Developmental Exposure Alcohol Research Center, Center for Developmental and Behavioral Neuroscience, Binghamton University – SUNY, Binghamton, NY, USA

    Mary B. Spodnick & Anushree N. Karkhanis

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  1. Paige M. Estave
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  2. Mary B. Spodnick
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Correspondence to Anushree N. Karkhanis.

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  1. Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

    Lee-Yuan Liu-Chen

  2. Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

    Saadet Inan

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Estave, P.M., Spodnick, M.B., Karkhanis, A.N. (2020). KOR Control over Addiction Processing: An Exploration of the Mesolimbic Dopamine Pathway. In: Liu-Chen, LY., Inan, S. (eds) The Kappa Opioid Receptor. Handbook of Experimental Pharmacology, vol 271. Springer, Cham. https://doi.org/10.1007/164_2020_421

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