IRI-514, A SYNTHETIC PEPTIDE ANALOG OF THYMOPENTIN, REDUCES THE BEHAVIORAL-RESPONSE TO SOCIAL STRESS IN RATS

Thymopentin, a synthetic pentapeptide (Arg-Lys-Asp-Val-Tyr) correspond ing to amino acids 32-36 of the thymic polypeptide thymopoietin, has b een reported to block adrenocorticotrope responses to stress. The purp ose of the present study was to explore potential antistress propertie s of a synthetic analogue of thymopentin, IRI-514 (Ac-Arg-Pro-Asp-Phe- NH2) using a behavioral response to a stressor. The behavioral respons e to social conflict stress (resident-intruder paradigm) was evaluated by the elevated plus-maze test of anxiety in adult Wistar rats. A sin gle subcutaneous (SC) administration of IRI-514, 48 h before stress, d ose-dependently reversed the anxiety-like behavior induced by the soci al 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-lastin g 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.