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 of neurotropic effects, including effects on learning and memory processes, neuroprotection, emotional state and pain sensitivity. Present work is aimed to compare the effects of peptides, the structure of which includes a natural fragment of ACTH and a stabilizing tripeptide PGP. The peptides ACTH4-7PGP (Semax), ACTH6-9PGP и ACTH7-10PGP were used in the work. The effects of these peptides on the exploratory behavior, anxiety level and pain sensitivity of white rats, as well as on the protein levels of the neurotrophic factors BDNF (brain derived neurotrophic factor) and VEGF (vascular endothelial growth factor) in primary neuron cultures were studied. A comparative study of the effects of analogs of different ACTH/MSH fragments revealed both similarities and differences in their neurotropic activity. The peptides structure of which includes a sequence of ACTH4-7 or ACTH6-9 have nootropic, anxiolytic and analgesic activity, and also cause an increase in VEGF levels in the culture of hippocampal neurons. The peptide containing the ACTH7-10 sequence in the structure exhibits anxiolytic activity, increases exploratory behavior, does not affect pain sensitivity and has a stimulating effect on BDNF and VEGF levels in neuronal cultures. The data obtained indicate that different parts of the N-terminal region of the ACTH molecule are responsible for the manifestation of certain neurotropic effects of melanocortins. The results of the study can be used in the development of therapeutics based on natural melanocortins.