Neuropeptide S counteracts 6-OHDA-induced motor deficits in mice

Julia J Didonet; Judney C Cavalcante; Lisiane de S Souza; Miriam S M O Costa; Eunice André; Vanessa de P Soares-Rachetti; Remo Guerrini; Girolamo Calo'; Elaine C Gavioli

doi:10.1016/j.bbr.2014.03.002

Neuropeptide S counteracts 6-OHDA-induced motor deficits in mice

Behav Brain Res. 2014 Jun 1:266:29-36. doi: 10.1016/j.bbr.2014.03.002. Epub 2014 Mar 11.

Authors

Julia J Didonet¹, Judney C Cavalcante², Lisiane de S Souza¹, Miriam S M O Costa², Eunice André³, Vanessa de P Soares-Rachetti¹, Remo Guerrini⁴, Girolamo Calo'⁵, Elaine C Gavioli⁶

Affiliations

¹ Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
² Laboratory of Neuroanatomy, Department of Morphology, Biosciences Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
³ Department of Pharmacology, Federal University of Parana, Curitiba, PR, Brazil.
⁴ Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.
⁵ Department of Medical Sciences, Section of Pharmacology, and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.
⁶ Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN, Brazil. Electronic address: egavioli@hotmail.com.

PMID: 24613977
DOI: 10.1016/j.bbr.2014.03.002

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.

Keywords: 6-OHDA; Dopamine; Motor activity; Mouse; Neuropeptide S; Parkinson disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenergic Agents / toxicity*
Analysis of Variance
Animals
Area Under Curve
Disease Models, Animal
Dopamine Agents / therapeutic use
Female
Levodopa / therapeutic use
Mice
Movement Disorders / drug therapy*
Movement Disorders / etiology*
Oxidopamine / toxicity*
Receptors, G-Protein-Coupled / therapeutic use*
Rotarod Performance Test
Substantia Nigra / metabolism
Substantia Nigra / pathology
Tyrosine 3-Monooxygenase / metabolism

Substances

Adrenergic Agents
Dopamine Agents
NPSR1 protein, human
Receptors, G-Protein-Coupled
Levodopa
Oxidopamine
Tyrosine 3-Monooxygenase