Orphan neuropeptide NocII, a putative pronociceptin maturation product, stimulates locomotion in mice

Florin, Sébastien; Suaudeau, Charles; Meunier, Jean‐Claude; Costentin, Jean

doi:10.1097/00001756-199702100-00025

Cited by 41 publications

(19 citation statements)

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“…Some of these, such as amphetamine (Young et al 1997), nociceptin (Florin et al 1997), and caffeine (Kaplan et al 1992), also stimulate rearing behavior. Other drugs, such as ethanol (Smoothy and Berry 1985), NocII (Florin et al 1997), and MK-801 (this study), suppress rearing behavior at doses that stimulate horizontal locomotion. This divergence of drug effects on the two types of locomotion is consistent with the idea that these two behaviors are mediated by different neural pathways.…”

Section: Discussionmentioning

confidence: 99%

Bimodal effects of MK-801 on locomotion and stereotypy in C57BL/6 mice

Zou

Strong

et al. 2004

Psychopharmacology

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Section: Discussionmentioning

confidence: 99%

Bimodal effects of MK-801 on locomotion and stereotypy in C57BL/6 mice

Zou

Strong

et al. 2004

Psychopharmacology

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“…NocII (Tocris, Bristol, United Kingdom) is an orphan neuropeptide that flanks NC in the precursor pro-NC. It may act through a novel specific receptor (42). Nocistatin (Tocris) is an endogenous peptide derived from the same precursor as NC and is able to block some NC-induced effects (43).…”

Section: Animals and Injectionsmentioning

confidence: 99%

Nociceptin/orphanin FQ exacerbates excitotoxic white-matter lesions in the murine neonatal brain

Laudenbach¹,

Calò²,

Guerrini³

et al. 2001

J. Clin. Invest.

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IntroductionPeriventricular leukomalacia (PVL) is a hemispheric white-matter lesion that is often cystic and occurs most frequently in infants born before 32 weeks of gestation (1). PVL is the major cause of cerebral palsy among premature infants (2). Based on epidemiological and experimental studies, the pathophysiology of PVL appears to be multifactorial. It potentially involves the combined toxicity of hypoxic-ischemic insults, excess free radicals, maternal-fetal infection with increased cytokine production, and growth factor deficiency (1,(3)(4)(5)(6)(7)(8). Excess release of glutamate and the subsequent overactivation of the excitotoxic cascade could represent a common molecular pathway for several of these risk factors (6, 9).Findings from several experimental studies support this hypothesis. Newborn mice injected intracerebrally with ibotenate, a glutamate analog acting mainly on N-methyl-D-aspartate (NMDA) receptors, develop periventricular cystic white-matter lesions mimicking several aspects of human PVL (10). In this well characterized murine model, several drugs that interfere with the excitotoxic cascade have been shown to be neuroprotective (7,(11)(12)(13)(14) while proinflammatory cytokines (15) and iron (16) exacerbated ibotenateinduced white-matter lesions. In order to further understand the pathophysiology of the ibotenateinduced cystic lesions, we targeted the NMDA receptors thought to be present on white-matter glial cells. Newborn mice were injected intracerebrally with sense, antisense, or missense oligonucleotides specific for the NMDA R1 receptor subunit (P. Gressens, unpublished work). The sequences of the oligonucleotides were identical to those previously used by Wahlestedt et al. in an in vitro assay (17). In newborn mice, pretreatment with antisense oligonucleotides was neuroprotective while control sense oligonucleotides had no effect on the ibotenate-induced lesion. Unexpectedly, missense oligonucleotides, which were used as another control, induced a threefold reduction in the severity of the excitotoxic whitematter lesions. A search of databases with Basic Local Alignment Search Tool (BLAST) revealed that 12 successive nucleotides of the so-called "NMDA R1 missense oligonucleotide" were actually complementary to a triplicated motif of the murine nociceptin (NC) mRNA, suggesting that the blockade of NC production is neuroprotective in the ibotenate model. Intracerebral administration of the excitotoxin ibotenate to newborn mice induces white-matter lesions, mimicking brain lesions that occur in human preterm infants. Nociceptin (NC), also called orphanin FQ, is the endogenous ligand of the opioid receptor-like 1 (ORL1) receptor and does not bind classical high-affinity opioid receptors. In the present study, administration of NC exacerbated ibotenate-induced white-matter lesions while coadministration of ibotenate with either of two NC antagonists reduced excitotoxic white-matter lesions by up to 64%. Neither ibotenate plus endomorphin I (a selective µ receptor agonist), nor ibot...

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“…However, in addition to N/OFQ, at least two other peptides are generated by the cleavage of ppN/OFQ, namely N/OFQ II and nocistatin (Mogil and Pasternak, 2001). These peptides do not bind the NOP receptor but exert biological activity (Fantin et al, 2007; Florin et al, 1997; Okuda-Ashitaka et al, 1998; Okuda-Ashitaka et al, 2012), questioning the view that endogenous N/OFQ is the only culprit for DA neurons degeneration observed in ppN/OFQ −/− mice.…”

Section: Introductionmentioning

confidence: 99%

Genetic and pharmacological evidence that endogenous nociceptin/orphanin FQ contributes to dopamine cell loss in Parkinson's disease

Arcuri

Viaro

Bido

et al. 2016

Neurobiology of Disease

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To investigate whether the endogenous neuropeptide nociceptin/orphanin FQ (N/OFQ) contributes to the death of dopamine neurons in Parkinson's disease, we undertook a genetic and a pharmacological approach using NOP receptor knockout (NOP−/−) mice, and the selective and potent small molecule NOP receptor antagonist (−)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111). Stereological unbiased methods were used to estimate the total number of dopamine neurons in the substantia nigra of i) NOP−/− mice acutely treated with the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), ii) naïve mice subacutely treated with MPTP, alone or in combination with SB-612111, iii) rats injected with a recombinant adeno-associated viral (AAV) vector overexpressing human mutant p.A53T α-synuclein, treated with vehicle or SB-612111. NOP−/− mice showed a 50% greater amount of nigral dopamine neurons spared in response to acute MPTP compared to controls, which was associated with a milder motor impairment. SB-612111, given 4 days after MPTP treatment to mimic the clinical condition, prevented the loss of nigral dopamine neurons and striatal dopaminergic terminals caused by subacute MPTP. SB-612111, administered a week after the AAV injections in a clinically-driven protocol, also increased by 50% both the number of spared nigral dopamine neurons and striatal dopamine terminals, and prevented accompanying motor deficits induced by α-synuclein. We conclude that endogenous N/OFQ contributes to dopamine neuron loss in pathogenic and etiologic models of Parkinson's disease through NOP receptor-mediated mechanisms. NOP receptor antagonists might prove effective as disease-modifying agents in Parkinson's disease, through the rescue of degenerating nigral dopamine neurons and/or the protection of the healthy ones.

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Orphan neuropeptide NocII, a putative pronociceptin maturation product, stimulates locomotion in mice

Cited by 41 publications

References 0 publications

Bimodal effects of MK-801 on locomotion and stereotypy in C57BL/6 mice

Bimodal effects of MK-801 on locomotion and stereotypy in C57BL/6 mice

Nociceptin/orphanin FQ exacerbates excitotoxic white-matter lesions in the murine neonatal brain

Genetic and pharmacological evidence that endogenous nociceptin/orphanin FQ contributes to dopamine cell loss in Parkinson's disease

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