The Effect of ACTH/MSH N-Terminal Fragment Analogs on the Anxiety Level, Pain Sensitivity and Levels of Neurotrophic Factors BDNF and VEGF in Primary Neuronal Cultures of Rats

ACTH/MSH-like peptides (melanocortins) have a wide range ofneurotropic effects, including effects on learning and memory processes,neuroprotection, emotional state and pain sensitivity. Present work isaimed to compare the effects of peptides, the structure of whichincludes a natural fragment of ACTH and a stabilizing tripeptidePGP. The peptides ACTH_4–7PGP (Semax), ACTH_6–9PGP,and ACTH_7–10PGP were used in the work. Theeffects of these peptides on the exploratory behavior, anxiety leveland pain sensitivity of white rats, as well as on the protein levelsof the neurotrophic factors BDNF (brain derived neurotrophic factor)and VEGF (vascular endothelial growth factor) in primary neuroncultures were studied. A comparative study of the effects of analogsof different ACTH/MSH fragments revealed both similarities and differencesin their neurotropic activity. The peptides structure of which includesa sequence of ACTH_4–7 or ACTH_6–9 havenootropic, anxiolytic and analgesic activity, and also cause an increasein VEGF levels in the culture of hippocampal neurons. The peptidecontaining the ACTH_7–10 sequence in the structureexhibits anxiolytic activity, increases exploratory behavior, doesnot affect pain sensitivity and has a stimulating effect on BDNFand VEGF levels in neuronal cultures. The data obtained indicatethat different parts of the N-terminal region of the ACTH moleculeare responsible for the manifestation of certain neurotropic effectsof melanocortins. The results of the study can be used in the developmentof therapeutics based on natural melanocortins.