title: Neuropeptide S counteracts 6-OHDA-induced motor deficits in mice.
abstract: Neuropeptide S (NPS) is a 20-aminoacid peptide that selectively activates a G-protein coupled receptor named NPSR. Preclinical studies have shown that NPSR activation promotes anxiolysis, hyperlocomotion, arousal and weakfullness. Previous findings suggest that dopamine neurotransmission plays a role in the actions of NPS. Based on the close relationship between dopamine and Parkinson disease (PD) and on the evidence that NPSR are expressed on brain dopaminergic nuclei, the present study investigated the effects of NPS in motor deficits induced by intracerebroventricular (icv) administration of the dopaminergic neurotoxin 6-OHDA in the mouse rotarod test. 6-OHDA injection evoked motor deficits and significantly reduced tyrosine hidroxylase (TH)-positive cells in the substantia nigra (SN) and ventral tegmental area. However, a positive correlation was found only between the motor performance of 6-OHDA-injected mice and the number of TH-positive cells in SN. The systemic administration of l-DOPA+benserazide (25+6.25 mg/kg) counteracted 6-OHDA-induced motor deficits in mice. Similar to L-DOPA, the icv injection of NPS (0.1 and 1 nmol) reversed motor deficits evoked by 6-OHDA. In conclusion, NPS attenuated 6-OHDA-induced motor impairments in mice assessed in the rota-rod test. We discussed the beneficial actions of NPS based on a putative facilitation of dopaminergic neurotransmission in the brain. Finally, these findings candidate NPSR agonists as a potential innovative treatment for PD.
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Didonet
authors.affiliation: Laboratory of Neuroanatomy, Department of Morphology, Biosciences Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Judney C
authors.initials: JC
authors.lastname: Cavalcante
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Lisiane de S
authors.initials: Lde S
authors.lastname: Souza
authors.affiliation: Laboratory of Neuroanatomy, Department of Morphology, Biosciences Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Miriam S M O
authors.initials: MS
authors.lastname: Costa
authors.affiliation: Department of Pharmacology, Federal University of Parana, Curitiba, PR, Brazil.
authors.forename: Eunice
authors.initials: E
authors.lastname: André
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
authors.forename: Vanessa de P
authors.initials: Vde P
authors.lastname: Soares-Rachetti
authors.affiliation: Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Department of Medical Sciences, Section of Pharmacology, and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calo'
authors.affiliation: Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil. Electronic address: egavioli@hotmail.com.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Gavioli
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000627:therapeutic use; D005260:Female; D007980:Levodopa / Q000627:therapeutic use; D051379:Mice; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology*; D016627:Oxidopamine / Q000633:toxicity*; D043562:Receptors, G-Protein-Coupled / Q000627:therapeutic use*; D045442:Rotarod Performance Test; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D015259:Dopamine Agents; C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled; D007980:Levodopa; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: 6-OHDA; Dopamine; Motor activity; Mouse; Neuropeptide S; Parkinson disease