Abstract
The aim of study – to investigate in depth the anxiolytic properties of nonapeptide NP9 in mice and rats, to find out its effect on the content of neuroactive amino acids in the brain. The experiment was carried out on 45 white random bread mice (24 females, 21 males) and 24 white random bread male rats. Nonapeptide NP9 was administered intranasally at a dose of 0.2 mg/kg to mice and at doses of 0.05 and 0.1 mg/kg to rats. Semax (Peptogen, Russia) at a dose of 0.1 mg/kg intranasally to mice and gidazepam (Gidazepam IC, Interkhim, Ukraine) at a dose of 5 mg/kg intragastrically to rats were used as reference drugs. Behavioral responses were studied in the open field and elevated plus maze tests in mice. Anxiolytic properties were also studied in the H. G. Vogel conflict test on rats. The content of glycine, GABA, glutamate, and aspartate in the brain of mice was determined. Nonapetide NP9 significantly reduced animal anxiety without motor suppression or any signs of sedation in the both tests open field and elevated plus maze, which is consistent with the results of previous studies in rats. Its anxiolytic activity was more stable than that of Semax. In the H. G. Vogel conflict test in rats, the anxiolytic properties of nonapeptide were confirmed in the dose range of 0.05 to 0.1 mg/kg; in terms of anti-anxiety properties, it was not inferior to gidazepam at a dose of 5 mg/kg. After a three-day intranasal administration of NP9 (0.2 mg/kg) to mice, the content of glutamate and aspartate in the brain homogenate increased while the content of glycine and GABA decreased. Thus, the anxiolytic properties of nonapeptide NP9 have been confirmed both in mice and rats. Its action is anxioselective, since it is not accompanied by a general depression of animals. After a three-day intranasal administration to mice, the studied nonapeptide increases the content of glutamate and aspartate, and also reduces the content of glycine and GABA in the brain.