Blockade of Nociceptin/Orphanin FQ Transmission Attenuates Symptoms and Neurodegeneration Associated with Parkinson's Disease
| Autor: | Brian M. Cox, Martina Fantin, Severo Salvadori, Flora Mela, Beata Buzas, Patrizia Romualdi, Rainer K. Reinscheid, Michele Morari, Michele Simonato, Sanzio Candeletti, Manuela Di Benedetto, Silvia Zucchini, Remo Guerrini, Jeffrey M. Brown, Jassir Witta, Matteo Marti |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Parkinson's disease Microdialysis NOP Substantia nigra J-113397 Neuroprotection Nociceptin UFP-101 Pharmacology Synaptic Transmission Levodopa Rats Sprague-Dawley Mice Dopamine Neurobiology of Disease medicine Animals Mice Knockout Chemistry General Neuroscience Parkinsonism Neurodegeneration Glutamate receptor Parkinson Disease medicine.disease Rats Mice Inbred C57BL Nociceptin receptor Opioid Peptides 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Nerve Degeneration Neuroscience medicine.drug |
| Zdroj: | The Journal of Neuroscience. 25:9591-9601 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2546-05.2005 |
| Popis: | The opioid-like neuropeptide nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP) are expressed in the substantia nigra (SN), a brain area containing dopamine neurons that degenerate in Parkinson's disease. Endogenous N/OFQ facilitates nigral glutamate release and inhibits nigrostriatal dopamine transmission and motor behavior. Here, we present evidence suggesting that endogenous N/OFQ may contribute to Parkinson's disease. Pharmacological blockade of the SN N/OFQ-NOP receptor system attenuated parkinsonian-like akinesia/hypokinesia in 6-hydroxydopamine hemilesioned or haloperidol-treated rats, whereas deletion of the NOP receptor gene conferred mice partial protection from haloperidol-induced motor depression. The antiparkinsonian action of NOP receptor antagonists was associated with reduction of glutamate release in the SN. In 6-hydroxydopamine hemilesioned rats, enhancement of N/OFQ expression and release was detected in the lesioned compared with the unlesioned SN, indicating that parkinsonism may be associated with overactivation of the N/OFQ-NOP receptor system in the SN. Finally, deletion of the N/OFQ gene conferred mice partial protection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced loss of SN dopamine neurons. Based on these data, we propose that NOP receptor antagonists may represent a novel approach for combined (symptomatic and neuroprotective) therapy of Parkinson's disease. |
| Databáze: | OpenAIRE |
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