Effects of fragment acth(15-18) and its analog acth(15-18)pgp on the cons.quences of the acute stress exposure

Tetrapeptide KKRR, corresponding to the fragment ACTH(15-18), is the shortest fragment that binds to the ACTH receptor with high affinity, does not activate this receptor and prevents the binding of the whole hormone molecule, therefore, exhibits the properties of an ACTH receptor antagonist. The aim of the work was to study the effects of the peptide ACTH(15-18) (KKRR) and its analogue ACTH(15-18)PGP on the animal behavior in normal conditions and after acute stress induced by inescapable electric foot-shock. It has been shown that the peptides do not affect the anxiety level of Wistar rats in the norm. Pretreatment with ACTH(15-18) (250 mu g/kg) and its analog ACTH(15-18)PGP (50 and 250 mu g/kg) significantly decreases anxiety level in rats exposed to the acute electric footshock and attenuates stress-induced changes in serum corticosterone. The magnitude and duration of the anti-stress effects of the peptide ACTH(15-18)PGP significantly exceeds the magnitude and duration of the effects of its natural prototype.