Vol 14, No 2 (2023)

In our previous work, we suggested that analogs of mammalian kisspeptin Kiss1 reduce anxiety and phobic reactions novel in Danio rerio. The most effective dose for the action of the studied analogs of kisspeptin corresponded to 0.1 mg per 1000 mL of water. In this study, other analogs of mammalian Kiss1 at a dose of 0.1 mg per 1000 mL of water also reduced the anxious behavior of Danio fish. The effect of Kiss1 and Kiss2 kisspeptins on the behavior of Danio rerio was also evaluated. In the novel test, the number of freezing decreased by two times with the introduction of kisspeptin 10 and by three times after the introduction of the kisspeptin analog. An analog of mammalian kisspeptin reduced the freezing time by two times. The length of the trajectory decreased by two times under the influence of the mammalian Kiss1 kisspeptin analog. With the action of kisspeptin 10, the number of transitions to the upper part of the tank increased by two times. After the introduction of the kisspeptin analog, the number of transitions to the upper part of the aquarium increased by three times. In the predator test, the number and time of freezing decreased by 1.5 times with the action of mammalian kisspeptins. The length of the trajectory after the introduction of kisspeptin bony fish and kisspeptin 10 mammals increased. The length of the trajectory after the introduction of Kiss1 increased by 1.5 times. The length of the trajectory after the introduction of Kiss2 increased by three times. After the introduction of kisspeptin 10, the trajectory increased by two times, and the time spent in the lower part of the tank decreased by two times. Kisspeptins of bony fish also reduced the anxiety and phobic reactions in fish, but to a lesser extent. Thus, kisspeptin 10 and an analog of mammalian kisspeptin in response to the presentation of a predator had more significant effects on anxiety in Danio rerio compared with the action of kisspeptin bony fish Kiss1 and Kiss2. Thus, bony fish kisspeptins and mammalian kisspeptins can reduce anxiety and phobic reactions in Danio rerio; however, mammalian kisspeptins are the most effective. Bony fish kisspeptin Kiss1 has an anxiolytic effect in contrast to Kiss2, which suggests that it affects fear reduction, and Kiss2 appears to be responsible for social and sexual behavior. The results support the hypothesis that kisspeptins may be involved in the regulation of anxiety and phobic states, apparently to maintain the emotional aspects of reproductive behavior, such as sexual motivation and arousal.

BACKGROUND: Folic acid is crucial for vital activities in both macro- and microorganisms. It is necessary for methylation, nucleotide synthesis, methionine formation, and reduction of the toxic effects of homocysteine. The addition of synthetic folic acid to the diet of pregnant women and those at pre-pregnancy preparation significantly reduced the risks of fetal neural tube defects, heart defects, and defects in other organs and systems. Folic acid can also help improve fertility potential. However, adverse effects of folic acid proficite on the health of older adults (asymptomatic B12-deficient status) and offspring of mothers taking high doses prescribed by medical specialists were reported, such as risks of infectious, inflammatory, and allergic diseases of the upper respiratory tract in children, eczema, psychomotor developmental disorders, and insulin resistance. In 1980, the direct excitatory effect of folic acid on synaptic transmission in the central nervous system was confirmed. This is due to the molecular structure because it contains L-glutamate.

AIM: To prove the correlation among probable neuropathologies, including a reduced threshold of seizures, a high risk of epilepsy in a model of offspring of Wistar rats with high-dose folate throughout gestation, and pre-pregnancy preparation.

MATERIALS AND METHODS: Experiments on Wistar rats (n = 45) were conducted to determine the occurrence of the first convulsive event by introducing 20% caffeine solution at the rate of 100 mg/kg of weight intraperitoneally.

RESULTS: In the control group, the average clonus time was 1779.6 s; in the experimental group with a 1 mg/kg folic acid per diet dosage, it was 797.3 s; and in the second group with a 5 mg/kg folic acid per diet, it was 439.7 s (p < 0.01).

CONCLUSION: The difference in the convulsive threshold may be due to changes in synaptic density following excess levels of synthetic folic acid during neural tube formation and subsequently during the differentiation of nervous tissue in the central nervous system (particularly, in the third trimester with a massive appearance of glutamatergic receptors), which can affect neurogenesis and neural network formation.

The study presents the history of the development of the Department of Pharmacology of Medical and Surgical (since 1881 Military Medical) Academy with an emphasis on the second century of its existence (1899–2000). This period was marked by the improvement of both the teaching of the discipline, based on new pharmacological data, and the introduction of new methods of drug research. A significant event was the release of a two-volume edition of N.P. Kravkov’s Fundamentals of Pharmacology in 1904–1905, which was based on the introduction of the latest achievements of scientific knowledge in the field of pharmacology. The textbook N.P. Kravkov withstood 14 editions (the last one was published in 1936, 12 years after the author’s death) and served as a model for the creation of all subsequent domestic textbooks and manuals on pharmacology in the 20th century. In experimental pharmacology, the method of isolated organs (N.P. Kravkov et al.) has been widely used as a universal method for quantifying pharmacological effects. In the 1920s, ideas about the synaptic effect of drugs were actively introduced (S.V. Anichkov et al.), and the effects of N-cholinergic drugs realized through the sinocarotid zone of the carotid artery were discovered and studied. Biochemical studies began to be widely used, which started with the works of N.P. Kravkov and continued by N.V. Lazarev, V.M. Vinogradov, and A.V. Smirnov. Clinical pharmacology was created and promoted after the discovery and first use of the intravenous anesthetic hedonal (N.P. Kravkov), particularly developed in the studies by N.V. Lazarev and V.M. Vinogradov. New ideas about antihypoxants and actoprotectors were formulated (V.M. Vinogradov) to increase combat capability and was successfully used in military pharmacology at the end of the 20^th century (V.M. Vinogradov and A.V. Smirnov). Therefore, with these achievements, the department has succeeded in both the academic and scientific fields.

BACKGROUND: One of the unresolved problems in improving the pharmacotherapy of central nervous system diseases is the development and creation of technologies that allow drugs to cross the blood–brain barrier. One way to bypass the blood–brain barrier is the intranasal route of administration. Drug delivery is influenced by the peculiarities of the mechanism of transport of substances.

AIM: To examine the effect of intranasal administration of oxytocin on the behavior of mice and its content in various brain structures.

MATERIALS AND METHODS: The study used 60 outbred mice divided into six groups. Group 1 were healthy and did not receive oxytocin or physiological solution, groups 2 and 3 received single injection of 20 and 300 µL of oxytocin 5 IU intraperitoneally, respectively, group 4 was injected intranasally with 20 µL of oxytocin 5 IU, group 5 received 20 µL of saline intranasally, and group 6 received 300 µL of saline intraperitoneally. Behavioral effects were recorded in the elevated plus maze for 5 min, and the duration of stay in the open arm, number of transitions between the arms, and number of hangings from the arms were assessed. The concentration of oxytocin was measured in the following structures: olfactory bulb, striatum, hypothalamus, and hippocampus using an enzyme immunoassay.

RESULTS: Intranasal administration of oxytocin causes changes in behavior in mice, particularly a decrease in the degree of anxiety (anxiolytic effect). When timing the open arms in the plus maze test, mice administered intranasal oxytocin spent more time in the arms (32.44 ± 4.28 versus the control group with 5.66 ± 1.96 s), the number of transitions between the sleeves increased (1.90 ± 0.10 s versus 1.10 ± 0.10 s in the control group), and number of hangings from the sleeves increased (8.44 ± 1.37 versus 3.77 ± 0.98 in the control group). An increase was noted in one of the indicators — number of hangings from the sleeve after intraperitoneal injection of 300 µL of oxytocin, which may indicate the anxiolytic effect of oxytocin. The remaining groups receiving intranasal saline injection, intraperitoneal saline injection, and intraperitoneal injection of 20 µL of oxytocin did not show significant changes in behavior compared with the control group. In addition, after intranasal administration of oxytocin, its content increased in certain brain structures, i.e., the hypothalamus and hippocampus.

CONCLUSION: The results of this study indicate the potential efficacy of intranasal administration of oxytocin in the treatment of diseases affecting the central nervous system.

BACKGROUND: Mining grate prickly (Orostachys spinosa (L.) Sweet) is a perennial herb of the Crassulaceae family that is widely used in folk medicine fresh as a decoction for epilepsy and sedative for nervous disorders.

AIM: To examine the effect of O. spinosa dry extract on the white rat behavior in tests with positive reinforcement.

MATERIALS AND METHODS: Experiments were conducted on 82 Wistar rats. The O. spinosa dry extract effects at doses of 50, 100, and 200 mg/kg on animal behavior were assessed in the hypophagy and T-maze tests.

RESULTS: Following the introduction of O. spinosa extract at doses of 100 and 200 mg/kg, the number of animals fed in the hypophagy test was 1.6 and 1.8 times greater than that in the control, and the feed volume exceeded by 94% and 78%, respectively, the indicator in the control group. On day 4 of training, a conditioned reflex was observed in 100% of the animals treated with 200 mg/kg O. spinosa extract. Following the administration of the O. spinosa extract at a dose of 100 mg/kg and the reference drug, a conditioned reflex was observed in 63% and 71% of the animals, respectively, which was 2.0 times higher than that in the control group.

CONCLUSION: The 100 and 200 mg/kg O. spinosa dry extracts positively affected the removal of the anxiety level, promoted an increase in orienting–exploratory activity, and thereby accelerated the development of a conditioned reflex in white rats.