Effects of Peptides ACTH6–9 PGP and ACTH4–7-PGP on Anxiety Levels in Rats in Punished and Unpunished Behavior

Abstract

Melanocortins form a class of regulatory peptide currently under active study; these include such biologically active substances as adrenocorticotropic hormone (ACTH) and α- β-, and γ-melanocyte-stimulating hormone (MSH). ACTH fragments, like other peptides of the melanocortins family, have marked neurotropic effects, particularly stimulating learning, memory, and attention processes. The active center of ACTH required for activation of all types of melanocortin receptor, is the sequence His-Phe-Arg-Trp and corresponds to fragment ACTH6–9. We report here studies of the synthetic peptide ACTH6–9-PGP, whose structure contains the natural fragment ACTH6–9 stabilized at the C terminal by attachment of the amino acid sequence prolyl-glycyl-proline (PGP) to increase resistance to the actions of carboxypeptidases. The effects of i.p. administration of ACTH6–9-PGP at doses of 0.5, 5, 50, 150, and 450 μg/kg as single does 15 min before assessment of anxiety levels in rats in the Vogel confl ict situation test (punished behavior) and the elevated plus maze (unpunished behavior) were studied. The effects of ACTH6–9-PGP in these tests were compared with those of its structural analog ACTH4–7-PGP at doses of 50, 150, and 450 μg/kg. The results showed that ACTH6–9-PGP in the Vogel conflict situation test increased anxiety levels in rats, which was apparent as decreases in drinking time (at all doses) and reductions in the number of licks (at doses of 0.5 and 150 μg/kg) (p < 0.01). ACTH6–9-PGP had no significant effect on the rats’ behavior in the elevated plus maze. ACTH4–7-PGP had no effects in the models of punished and unpunished behavior. Thus, ACTH6–9-PGP, in contract to ACTH4–7-PGP, was found to affect anxiety levels in rats, depending on the dose of peptide and the behavioral model used.