In experiments on male Wistar rats, the effect of synthetic derivatives of arginine-vasopressin (tetrapeptides N-Ac-DSer-Pro-DArg-Gly-NH2 (I) (1.0 μg/kg, i. n.), N-Ac-Trp -Pro-Arg-Gly-NH2 (II) (1.0 μg/kg, i. n.) on the dynamics of the level of anxiety (LA) and the ability to reproduce operant reactions (OR) against the background of 24-hour deprivation of the paradoxical phase of sleep (REM sleep deprivation) in rats. Statistically, N-Ac-Trp-Pro-Arg-Gly-NH2 significantly ( p < 0.05) reduced the LA of rats exposed to stress, increasing the proportion of individuals in the population that had spent time in the central square of the actometer chamber not less than 10 % of the total duration of actometry. The oligopeptide N-Ac-DSer-Pro-DArg-Gly-NH2 had a statistically significant ( p < 0.05) corrective effect on the ability to reproduce the developed OR of pressing the pedal in rodents (Wistar rats of an unranked population and Wistar individuals with low LA) subjected to REM sleep deprivation. Thus, both studied compounds did not cause cognitive impairment, and N-Ac-DSer-ProDArg-Gly-NH2 improved mnestic functions against the background of REM sleep deprivation. The results of assessing the level of general motor activity indicated the absence of side sedative effects in I (1.0 μg/kg) and II (1.0 μg/kg ‒ at a dose that causes an anxiolytic effect when administered II). The data obtained indicate the anxiolytic effect of N-Ac-Trp-Pro-Arg-GlyNH2, the positive mnemotropic effect of N-Ac-DSer-Pro-DArg-Gly-NH2, and a low likelihood of developing side effects in relation to the central nervous system against the background their applications.
The effect of proline-containing oligopeptides N-Ac-DSer-Pro-DArg-Gly-NH 2 (B-4), N-Ac-Trp-Pro-Arg-Gly-NH 2 (B-5), N-Ac-Tyr-Pro-Arg-Gly-NH 2 (B-7), and Pro-Gly on the behavior of male ICR mice in the Forced Swim Test was studied. N-Ac-DSer-Pro-DArg-Gly-NH 2 (1.0 mcg/kg, i.n) increased the intensity of active swimming, most pronounced – during the last 2 minutes of testing (maximum fatigue period), i.e., it prevented the behavior of “despair”.
A search for novel antidepressant analogs of arginine-vasopressin (AVP) by a computer modeling revealed the following peptide analogs of the C-terminal part of AVP: N-Ac-D-Ser-Pro-D-Arg-Gly-NH2, N-Ac-Phe-Pro-Arg-Gly-NH2, and N-Ac-Trp-Pro-Arg-Gly-NH2. Syntheses of the modeled compounds were described in this article. The compounds that could potentially exhibit the antidepressant activity were examined in the forced swimming test. N-Ac-Trp-Pro-Arg-Gly-NH2 (0.1, 1.0, and 10.0 µg/kg) and N-Ac-D-Ser-Pro-D-Arg-Gly-NH2 (1.0 µg/kg) were shown to have the highest similarity to the fluoxetine reference antidepressant according to a number of parameters after the intranasal administration to the Wistar male rats.
The article presents the synthesis and results of the study of the effect of chronic neonatal administration by intranasal method of an analogue of the C-terminal fragment of arginine-vasopressin (AVP) - N-Ac-DMet-Pro-Arg-Gly-NH2 on the training and level of depression in white rats of three age groups. It is shown that the most significant effect of the analogue was manifested in the test for the development of conditional reaction of active avoidance. A favorable effect on the degree of depression of animals is also well expressed. According to the data obtained, we conclude that the action of the peptide is manifested only under the influence of a biologically significant stimulus.
The article presents the synthesis and results of the study of the effect of chronic neonatal administration by intranasal method of an analogue of the C-terminal fragment of arginine-vasopressin (AVP) - N -Ac- D Met-Pro-Arg-Gly-NH 2 on the training and level of depression in white rats of three age groups. It is shown that the most significant effect of the analogue was manifested in the test for the development of conditional reaction of active avoidance. A favorable effect on the degree of depression of animals is also well expressed. According to the data obtained, we conclude that the action of the peptide is manifested only under the influence of a biologically significant stimulus.