title: 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.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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).
  
  
  METHODS
  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).
  
  
  RESULTS
  SR142801 (100 pmol) or SP6-11(C-terminal) (10 pmol) 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 (10 pmol) 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 (1 pmol) was prevented by SP6-11.
  
  
  CONCLUSIONS
  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.
authors: Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, PE 50670-901, Brazil. Electronic address: duartefilipe@hotmail.com.
authors: Filipe Silveira
authors: FS
authors: Duarte
authors: Department of Physiology and Pharmacology, Federal University of Alagoas, Maceió, AL 57020-720, Brazil.
authors: Marcelo
authors: M
authors: Duzzioni
authors: Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC 88049-900, Brazil.
authors: Leandro Rinaldi
authors: LR
authors: Leme
authors: Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC 88049-900, Brazil.
authors: Saulo de Paiva
authors: Sde P
authors: Smith
authors: Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC 88049-900, Brazil.
authors: Thereza C M
authors: TC
authors: De Lima
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D010880:Piperidines; D018042:Receptors, Neurokinin-3; C054724:senktide; D013373:Substance P; C032292:substance P (6-11); C091554:SR 142801; D011761:Pyrrolidonecarboxylic Acid
keywords: Anxiety; Elevated plus-maze; NK(3) receptors; SP6-11(C-terminal); SR142801; Senktide