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NOP Receptor Ligands and Parkinson’s Disease

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The Nociceptin/Orphanin FQ Peptide Receptor

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 254))

Abstract

Nociceptin/Orphanin FQ (N/OFQ) and its NOP receptor are highly expressed in motor areas of the rodent, nonhuman, and human primate brain, such as primary motor cortex, thalamus, globus pallidus, striatum, and substantia nigra. Endogenous N/OFQ negatively regulates motor behavior and dopamine transmission through NOP receptors expressed by dopaminergic neurons of the substantia nigra compacta. Consistent with the existence of an N/OFQ tone over dopaminergic transmission, blockade of NOP receptor antagonists increases striatal dopamine release. In this chapter, we will review the evidence linking the N/OFQ-NOP receptor system to Parkinson’s disease (PD). We will first discuss data showing that the central N/OFQ-NOP receptor system undergoes plastic changes in different basal ganglia nuclei following dopamine depletion. Then we will show that NOP receptor antagonists relieve motor deficits in different rodent and nonhuman primate models of PD. Mechanistically, NOP receptor blockade in substantia nigra reticulata results in rebalancing of the inhibitory GABAergic and excitatory glutamatergic inputs impinging on nigro-thalamic GABAergic neurons, leading to thalamic disinhibition. We will also present data showing that, in addition to motor symptoms, N/OFQ also plays a role in the parkinsonian neurodegeneration. In fact, NOP receptor antagonists possess neuroprotective/neurorescue properties in in vitro and in vivo models of PD.

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Authors and Affiliations

  1. Department of Medical Sciences, Section of Pharmacology, and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy

    Daniela Mercatelli, Clarissa Anna Pisanò, Salvatore Novello & Michele Morari

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  1. Daniela Mercatelli
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  2. Clarissa Anna Pisanò
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  3. Salvatore Novello
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  4. Michele Morari
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Correspondence to Michele Morari .

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Editors and Affiliations

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

    Mei-Chuan Ko

  2. Department of Medical Sciences, Section of Pharmacology, University of Ferrara, Ferrara, Italy

    Girolamo Caló

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Mercatelli, D., Pisanò, C.A., Novello, S., Morari, M. (2018). NOP Receptor Ligands and Parkinson’s Disease. In: Ko, MC., Caló, G. (eds) The Nociceptin/Orphanin FQ Peptide Receptor. Handbook of Experimental Pharmacology, vol 254. Springer, Cham. https://doi.org/10.1007/164_2018_199

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