Evidence for involvement of NK3 receptors in the anxiogenic-like effect of SP6-11(C-terminal), a metabolite of substance P, in rats evaluated in the elevated plus-maze

• Published in: Behavioural brain research 2016-04, Vol.303, p.168-175
• Main Authors: Duarte, Filipe Silveira, Duzzioni, Marcelo, Leme, Leandro Rinaldi, Smith, Saulo de Paiva, De Lima, Thereza C.M.
• Format: Article
• Language: English
• Subjects: Animals; Anxiety; Anxiety - metabolism; Elevated plus-maze; Male; NK3 receptors; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Piperidines - administration & dosage; Pyrrolidonecarboxylic Acid - administration & dosage; Pyrrolidonecarboxylic Acid - analogs & derivatives; Pyrrolidonecarboxylic Acid - pharmacology; Rats; Rats, Wistar; Receptors, Neurokinin-3 - agonists; Receptors, Neurokinin-3 - antagonists & inhibitors; Receptors, Neurokinin-3 - physiology; Senktide; SP6-11(C-terminal); SR142801; Substance P - administration & dosage; Substance P - analogs & derivatives; Substance P - metabolism; Substance P - pharmacology
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2016.02.003

•Rats were i.c.v. treated with SR142801 (NK3 receptors antagonist) one minute to prior vehicle or SP6-11(C-terminal).•Other groups received SP6-11(C-terminal) i.c.v. one minute prior to senktide (NK3 receptors agonist) or vehicle.•The animals were behaviorally evaluated in the elevated plus-maze test (EPM).•SR142801 or SP6-11(C-terminal) promoted anxiogenic-like effects. Senktide promoted an anxiolytic-like profile.•SR142801 potentiated the SP6-11-induced anxiety. The anxiolytic-like effect induced by senktide was prevented by SP6-11. Substance P (SP) is a neuropeptide widely expressed throughout the fear-processing pathways of the brain. SP is cleaved by several proteolytic enzymes in amino (N-) and carboxy (C-) terminal sequences, which can have biological activities per se. We have previously shown that the anxiogenic-like effects elicited by SP6-11(C-terminal), a specific metabolite of SP, are mediated via NK1 and NK2 receptors. Nevertheless, there are evidences that C-terminal fragments may have a greater affinity for NK3 receptors. The aim of the present study was to further investigate the possible involvement of NK3 receptors in the anxiogenic-like effects induced by SP6-11(C-terminal). Adult male Wistar rats were intracerebroventricularly (i.c.v.) treated with SR142801 (NK3 receptors antagonist) or vehicle one minute to prior SP6-11(C-terminal) or vehicle. Other experimental groups received SP6-11(C-terminal) or vehicle i.c.v. one minute prior to senktide (NK3 receptors agonist) or vehicle. After five minutes, the animals were behaviorally evaluated in the elevated plus-maze test (EPM). SR142801 (100pmol) or SP6-11(C-terminal) (10pmol) reduced all the parameters of open-arms exploration and increased the number of protected stretch-attend postures in the EPM, indicating an anxiogenic-like effect. Senktide (10pmol) promoted an opposite effect on these behavioral parameters, characterizing an anxiolytic-like profile. Pretreatment with SR142801, in an ineffective dose, potentiated the SP6-11-induced anxiety, especially in the unprotected head-dipping and protected stretch-attend postures behaviors. Moreover, the anxiolytic-like effect induced by senktide (1pmol) was prevented by SP6-11. Our results give support to the involvement of NK3 receptors in the anxiogenic-like actions of SP6-11(C-terminal), where this metabolite seems to behave as an antagonist, in a way similar to SR142801.