Влияние пептидов АКТГ 6–9 -PGP и АКТГ 4–7 -PGP на уровень тревожности у крыс при наказуемом и ненаказуемом поведении

Abstract

One of the currently studied classes of regulatory peptides is melanocortins (MCs), which include biologically active substances such as adrenocorticotropic hormone (ACTH), α-, β- and γ-melanocyte stimulating hormones (MSH). ACTH fragments, like other peptides of the MC family, have pronounced neurotropic effects aimed, in particular, at stimulating the processes of learning, memory and attention. Moreover, the active ACTH center necessary for the activation of all types of melanocortin receptors is the His-Phe-Arg-Trp sequence corresponding to the ACTH6-9 fragment. In the present work, we studied a synthetic peptide, ACTH6-9-PGP, which contains a natural fragment ACTH6-9-PGP stabilized from the C-terminus with the amino acid sequence prolyl-glycyl-proline (PGP) to increase resistance to the action of carboxypeptidases. The effects of intraperitoneal administration of ACTH6-9-PGP at doses of 0.5; 5; 50; 150 and 450 µg/kg were studied once 15 minutes before the start of the experiment on studying the level of anxiety in rats using the Vogel conflict test (punished behavior) and the elevated plus maze test (unpunished behavior). The effects of ACTH6-9-PGP and its structural analogue, ACTH4-7-PGP at doses of 50, 150 and 450 µg/kg were compared using these tests. It was found that ACTH6-9-PGP in the Vogel conflict test led to an increase in the level of anxiety in rats, which manifested itself in a reduction in drinking time (in all doses) and a decrease in the number of licks (at doses of 0.5 and 150 μg/kg (p <0.01)). In the elevated plus maze test, ACTH6-9-PGP did not significantly affect rat behavior. In models of punished behavior and unpunished behavior, no effects of ACTH4-7-PGP were detected. Thus, it was found that ACTH6-9-PGP, in contrast to ACTH4-7-PGP, affects the level of anxiety in rats depending on the dose of the peptide and the model of behavior studied.