IRI-514, a synthetic peptide analogue of thymopentin, reduces the behavioral response to social stress in rats.
Thymopentin, a synthetic pentapeptide (Arg-Lys-Asp-Val-Tyr) corresponding to amino acids 32-36 of the thymic polypeptide thymopoietin, has been reported to block adrenocorticotrope responses to stress. The purpose of the present study was to explore potential antistress properties of a synthetic analogue of thymopentin, IRI-514 (Ac-Arg-Pro-Asp-Phe-NH2) using a behavioral response to a stressor. The behavioral response to social conflict stress (resident-intruder paradigm) was evaluated by the elevated plus-maze test of anxiety in adult Wistar rats. A single subcutaneous (SC) administration of IRI-514, 48 h before stress, dose-dependently reversed the anxiety-like behavior induced by the social stress. The effect of IRI-514 was present over an extended period (24-72 h) following SC administration and was maximally effective at a dose of 1 mg/kg. These results indicate that IRI-514 has a long-lasting modulatory effect on behavioral responses to a stressor, and suggest that thymopoietin-derived peptides may have a role in modulating both behavioral and neuroendocrine responses to stress.
Menzaghi
F
F
Scripps Research Institute, Department of Neuropharmacology, La Jolla, CA 92037, USA.
Heinrichs
S C
SC
Vargas-Cortes
M
M
Goldstein
G
G
Koob
G F
GF
D000374:Aggression / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D003220:Conflict, Psychological; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012931:Social Environment; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology; D016305:Thymopentin / Q000031:analogs & derivatives* / Q000494:pharmacology*
C102862:IRI 514; D007155:Immunologic Factors; D009842:Oligopeptides; D016305:Thymopentin