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Kappa Opioid Receptor Mediated Differential Regulation of Serotonin and Dopamine Transporters in Mood and Substance Use Disorder

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The Kappa Opioid Receptor

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

Abstract

Dynorphin (DYN) is an endogenous neurosecretory peptide which exerts its activity by binding to the family of G protein-coupled receptors, namely the kappa opioid receptor (KOR). Opioids are associated with pain, analgesia, and drug abuse, which play a central role in mood disorders with monoamine neurotransmitter interactions. Growing evidence demonstrates the cellular signaling cascades linked to KOR-mediated monoamine transporters regulation in cell models and native brain tissues. This chapter will review DYN/KOR role in mood and addiction in relevance to dopaminergic and serotonergic neurotransmissions. Also, we discuss the recent findings on KOR-mediated differential regulation of serotonin and dopamine transporters (SERT and DAT). These findings led to a better understanding of the role of DYN/KOR system in aminergic neurotransmission via its modulatory effect on both amine release and clearance. Detailed knowledge of these processes at the molecular level enables designing novel pharmacological reagents to target transporter motifs to treat mood and addiction and reduce unwanted side effects such as aversion, dysphoria, sedation, and psychomimesis.

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Acknowledgments

The work was supported by National Institutes of Health grants to SR (MH112731) and LDJ (DA045888).

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA

    Durairaj Ragu Varman, Lankupalle D. Jayanthi & Sammanda Ramamoorthy

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  1. Durairaj Ragu Varman
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  2. Lankupalle D. Jayanthi
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  3. Sammanda Ramamoorthy
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Correspondence to Lankupalle D. Jayanthi or Sammanda Ramamoorthy .

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Editors and Affiliations

  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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Ragu Varman, D., Jayanthi, L.D., Ramamoorthy, S. (2021). Kappa Opioid Receptor Mediated Differential Regulation of Serotonin and Dopamine Transporters in Mood and Substance Use Disorder. 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_2021_499

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