Abstract
Neuropeptide S (NPS) is the endogenous ligand of a G-protein-coupled receptor named as NPSR. Behavioral effects have been recently attributed to NPS, i.e. hyperlocomotion, anxiolysis, and wakefulness. However, little is known about the mechanisms by which NPS evokes such biological actions. The present study aimed to investigate the role played by the adenosine A2A and A1 receptors in hyperlocomotion induced by NPS. Spontaneous locomotion was assessed in an activity cage for 30 min in mice acutely treated with caffeine (a nonselective adenosine receptor antagonist), ZM241385 (a selective A2A receptor antagonist), or CPT (a selective A1 receptor antagonist) before NPS challenge (0.1 nmol, i.c.v.), which induce hyperlocomotion in mice. The pretreatment with caffeine (3 mg/kg, i.p.), in an inactive dose per se, prevented the increase in locomotion evoked by NPS. The co-administration of NPS (0.1 nmol, i.c.v.) and ZM241385 (0.1 pmol, i.c.v.) counteracted hyperlocomotion evoked by NPS. The co-administration of NPS and CPT (0.1 pmol, i.c.v.) slightly facilitated the increase in locomotion evoked by NPS alone. In summary, the pharmacological blockade of A2A receptors significantly attenuated the stimulatory effects of NPS. By contrast, the antagonism of A1 receptors facilitated NPS-induced hyperlocomotion in mice, but we cannot rule out a merely additive effect of two stimulatory systems in the brain. Altogether, this is the first evidence of a putative role played by A2A and A1 receptors in modulating hyperlocomotion induced by NPS.
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Acknowledgments
This work was supported by funds from International Brain Research Organization-IBRO (Return Home Fellowship to ECG), the Brazilian National Council Research (CNPq grants, no. 478249/2006-3 to CRB and 479760/2007 to ECG) and UNESC.
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Boeck, C.R., Martinello, C., de Castro, A.A. et al. Blockade of adenosine A2A receptor counteracts neuropeptide-S-induced hyperlocomotion in mice. Naunyn-Schmied Arch Pharmacol 381, 153–160 (2010). https://doi.org/10.1007/s00210-009-0480-2
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DOI: https://doi.org/10.1007/s00210-009-0480-2