Influence of Subchronic Administration of the HLDF-6 Peptide on an Efficacy of the Exploratory Behavior of Inbred Mice of the Balb/c and C57Bl/6 Strains

• Published in: Russian journal of bioorganic chemistry Vol. 47; no. 1; pp. 270 - 277
• Main Authors: Kovalev, G. I., Vasileva, E. V., Salimov, R. M., Zolotarev, Yu. A., Dadayan, A. K., Bogachouk, A. P., Lipkin, V. M.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2021; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Cognitive enhancement; Life Sciences; Organic Chemistry; Peptides; the HLDF-6 peptide; an efficacy of the exploratory behavior; nootropic activity; the radioreceptor analysis; closed cross maze
• ISSN: 1068-1620; 1608-330X
• DOI: 10.1134/S1068162021010118

A comparative analysis of the psychotropic activity of the HDLF-6 peptide in the acidic form (TGENHR) and the amide form (HLDF-6-amide, TGENHR-NH
2
) was carried out using the method for the behavioral assessing of inbred mice of the Balb/c strain (with initial deficiency of exploratory activity) and the С57Bl/6 strain (as reference) in the “closed cross-maze” test (CCM). The peptide forms were intraperitoneally (at the subchronic daily doses of 100 μg/kg,) and intranasally (at daily doses of 30, 100, and 300 μg/kg) administrated for five days. Both intraperitoneal and intranasal administration of HLDF-6-amide (but not the HLDF-6 peptide) were shown to result in a development of the selective nootropic effect in the Balb/c mouse population. On the contrary, this effect was not reproduced in the group of the C57Bl/6 mice. The locomotor activity and the anxiety level were not changed in these groups of mice after injections of both forms of the peptide. Based on the results of behavioral experiments in the CCM test, we concluded that the HLDF-6-amide exhibited a selective pharmacological effect, which manifested itself as an increase in the exploratory activity only for the animals with an initial cognitive deficit. This property was characteristic of nootropic drugs. We first established by the radioreceptor analysis that a common target for the specific high affinity binding on the rat cerebral membranes existed for the HLDF-6 peptide and its derivatives. Thus, further development of an original intranasal nootropic drug on the basis of the HLDF-6-amide was promising.