title: Blockade of adenosine A2A receptor counteracts neuropeptide-S-induced hyperlocomotion in mice.
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 A(2A) and A(1) 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 A(2A) receptor antagonist), or CPT (a selective A(1) 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 A(2A) receptors significantly attenuated the stimulatory effects of NPS. By contrast, the antagonism of A(1) 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 A(2A) and A(1) receptors in modulating hyperlocomotion induced by NPS.
authors.affiliation: Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Carina R
authors.initials: CR
authors.lastname: Boeck
authors.forename: Caroline
authors.initials: C
authors.lastname: Martinello
authors.forename: Adalberto A
authors.initials: AA
authors.lastname: de Castro
authors.forename: Morgana
authors.initials: M
authors.lastname: Moretti
authors.forename: Tiago
authors.initials: T
authors.lastname: Dos Santos Casagrande
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Girolamo
authors.initials: G
authors.lastname: Calo'
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Gavioli
mesh_terms: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D009479:Neuropeptides / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D009479:Neuropeptides; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C506531:neuropeptide S, human; D002110:Caffeine