It has been determined that approximately 10% of patients without cardiovascular disease undergoing non-cardiac surgery (NS) suffer myocardial injury (MI) and have a 10% risk of death within 30 days after Sur. Preoperative stress (PS) increases the risk of MI after NS (MINS). The mechanisms of MINS are not well understood. The consequence of many NS is physical inactivity with the development of weakness and fatigue. To date, the relationship between NS and changes in the morphofunctional state of muscles in the postoperative period has been poorly studied. This study reveals for the first time, that metabolic and hormonal changes induced by PS+NS, as well as NS itself and inhalational anesthesia in C57BL/6 mice, are causal factors underlying the mechanisms of MINS in the postoperative period. It was also discovered for the first time, that even low values of the triglyceride-glucose index can indicate ischemic/hypoxic damage of the myocardium and skeletal muscles. Preoperative stress significantly impaired morphofunctional state of the studied organs. More research is needed on the effects of PS and NS on myocardium and muscle performance, as well as the risks and benefits of perioperative treatment.

Abstract—Here we studied the effects of anti-epileptic substance GIZh-298 and the drug of comparison sodium valproate (NaV) on the contents of excitatory and inhibitory amino acids in the frontal cortex, hypothalamus, striatum, and hippocampus of the mouse brain in a model of generalized tonic-clonic seizures induced by maximal electroshock (MES). The levels of excitatory amino acids such as aspartate in the hypothalamus and glutamate in the hippocampus were decreased by 20.8 and 16.7

Approximately 10% of patients without cardiovascular disorders suffer myocardial injury and have a 10% risk of death within 30 days after noncardiac surgery. Preoperative stress increases the risk of myocardial injury after noncardiac surgery (MINS). The mechanisms of MINS are poorly understood. Lack of physical activity and the development of weakness and fatigue are consequences of many noncardiac surgery types. The relationship between surgery and changes in the morphofunctional state of muscles in the postoperative period is still unclear now. The study showed for the first time that metabolic and hormonal changes caused by preoperative stress + surgery or surgery alone underlie MINC in the postoperative period in C57BL/6 mice. Minor increases in triglyceride-glucose (TyG) index were for the first time identified as indicative of ischemic/hypoxic damage to the myocardium and skeletal muscles. More research is necessary to perform to better understand the effects of preoperative stress and noncardiac surgery on the myocardium and muscle performance, as well as the risks and benefits of perioperative treatment.

Recent studies have shown that the pineal gland hormone melatonin has a variety of regulatory effects of an adaptogen with multimodal capabilities. Currently, the properties of melatonin as an anticarcinogenic agent are being actively studied. Preclinical studies have demonstrated that melatonin in combination with chemotherapeutic agents is capable of producing a synergistic effect in combination therapy for the treatment of melanoma.

Abstract—The study of the status of norepinephrine-, dopamine- and serotonergic neurotransmitter systems of BALB/C mice brain structures on 15 and 64 days of postnatal development (PD) in the model of autistic disturbances induced by injection of sodium valproate (SV, 400 mg/kg , s/c) to pregnant females was carried out using the HPLC/ED method. The level of both catechol- and indolamines in the brain structures of control mice at the age of 15 days was significantly lower than in adult animals at the age of 64 days. Prenatal administration of SV caused a decrease in all parameters of monoaminergic neurotransmission in the striatum of offspring at the age of 15 days but had no effect in other brain structures studied. Subsequently, the level of dopamine increased and by the 64th day of PD did not differ from the parameters of the control group. The parameters of the serotonergic system changed in a similar pattern, with the content of serotonin and the serotonin metabolite 5-OIAA in the striatum increasing gradually and reaching maximum values by the 64th day of PD. Our data allows to assume that the administration of SV to pregnant females affects the activity of the dopamine and serotonergic systems of the brain of the offspring causing a decrease in their activity in the striatum by the 15th day of PD followed by restoration to control values by the 64th day, which we previously observed in male pups. Thus, the patterns of dynamic changes in the neurochemical profile do not differ between males and females.

The aim of the present work was to study the dynamics of neurotransmitter amino acids after acute Noopept (a dipeptide analogue of piracetam used in clinical practice as a nootropic agent) administration in intact and long-term ethanol (ETOH) exposed rats. Albino male rats were given 10% (vol/vol) ETOH solution as the only source of fluid 24 h / 7 days per week (n = 5). Also we used intact rats of the same age which had no access to ethanol (n = 5). The excitatory and inhibitory amino acids in the extracellular space of the dorsal hippocampus region in freely moving intact and ETOH-exposed rats during prolonged alcohol deprivation were measured using the intracerebral microdialysis method followed by HPLC/ED. There were no significant differences in the level of neurotransmitter amino acids between ETOH-exposed and intact animals. For the first time, in vivo experiments the effect of Noopept (1.5 mg/kg, i.p.) on the level of excitatory amino acids (an increase in ASP by 2.38 times and GLU by 2.28 times) along with an increase in the level of the inhibitory amino acid GLI by 3.13 times only in intact rats was shown. Thus, in ETOH-exposed rats under the adaptive rearrangements in prolonged ethanol withdrawal, the neurochemical mechanisms of the hippocampus seem to be characterized by insensitivity to an acute Noopept administration. Animal neurochemical studies of changes in the mediator amino acids due to the long-term effect of alcohol on the CNS may be of practical importance for the development of optimal strategies and pharmacotherapy.

Abstract—The aim of the present work was to study the dynamics of neurotransmitter amino acids after acute Noopept (a dipeptide analogue of piracetam used in clinical practice as a nootropic agent) administration in intact and long-term ethanol (ETOH) exposed rats. Albino male rats were given 10

We studied psychoemotional characteristics and the blood level of corticosterone in sexually mature male C57BL/6 mice (n=40): intact (control), after simulating preoperative stress and surgery, after surgery, and after anesthesia alone. It was found that the anxiety index calculated on the basis of testing in the elevated plus maze was significantly higher in both groups of operated animals. The mice of both operated groups and animals exposed to anesthesia alone showed increased anxiety. Symptoms indicating a high probability of transition of anxiety into a psychoemotional disorder have been recorded.

Установлено, что фенозановая кислота, являющаяся действующим началом препарата «Дибуфелон» и обладающая антиоксидантной активностью, усиливает противосудорожное действие классических противоэпилептических лекарственных средств – вальпроевой кислоты и карбамазепина. В тесте антагонизма с максимальным электрошоком фенозановая кислота обладает противосудорожным действием в диапазоне доз 120 – 320 мг/кг. При введении фенозановой кислоты и вальпроевой кислоты в неэффективных дозах (80 и 100 мг/кг соответственно) наблюдается появление противосудорожного эффекта. Фенозановая кислота в дозах, в которых это фармакологическое вещество оказывает противосудорожный эффект (120, 160 и 240 мг/кг), усиливает эффективность вальпроевой кислоты (100 и 150 мг/кг), что наблюдается по ослаблению тяжести судорожных проявлений (максимально в 2,3 раза по баллам) и устранению тонической экстензии конечностей. Наиболее выраженное потенцирующее действие фенозановой кислоты (160 мг/кг) выявляется в отношении эффекта карбамазепина (6,5 и 10 мг/кг): в данных комбинациях тяжесть судорожных реакций ослабевает (максимально в 4,5 раза по баллам) и отмечается полная защита от развития тонических судорог и генерализованных клонических реакций. Нейрохимический анализ показал, что фенозановая кислота повышает сниженные при МЭШ-индуцированных судорогах уровни тормозных аминокислот таурина и глицина в гипоталамусе и гиппокампе, а вальпроевая кислота увеличивает уровни ГАМК в гипоталамусе, восстанавливая баланс ГАМК/глутамат. Таким образом, фенозановая кислота, обладая противосудорожными свойствами, при фармакодинамическом взаимодействии с вальпроевой кислотой и карбамазепином потенцирует их противосудорожные эффекты.

The effects of acute swimming stress (ASS) on the behavioral and neurochemical actions of a pyrazolo[C]pyridine derivative GIZh-72 (20 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were studied. Increased anxiety reactions were seen in the open field test 1 h after ASS in BALB/c mice and the marble burying test in C57BL/6 mice. Weakening of anxiety reactions in BALB/c and C57BL/6 mice in the open field test and in C57BL/6 mice in the marble burying test was noted at 24 h. Serotonin levels increased and noradrenaline levels decreased in the hypothalamus of BALB/c and C57BL/6 mice 1 h after ASS, while the prefrontal cortex showed increases in noradrenaline, 3,4-dihydroxyphenylacetic acid, and the 3,4-dihydroxyphenylacetic acid/dopamine ratio in BALB/c mice. These changes correlated with increases in anxiety reactions, while their reversal in response to GIZh-72 and diazepam or 24 h after ASS coincided with weakening of anxiety reactions in mice. Diazepam and GIZh-72 weakened anxiety reactions in BALB/c and C57BL/6 mice in the open field and marble burying tests in the absence of stress. At 1 h after ASS, the effects of GIZh-72 were retained in BALB/c and C57BL/6 mice in the open field and marble burying tests, while the effects of diazepam persisted in C57BL/6 mice and increased in BALB/c mice in the open field test. At 24 h, the effects of GIZh-72 in the open field test increased in BALB/c mice but weakened and were accompanied by a tendency to a sedative action in C57BL/6 mice. The effects of diazepam in the open field increased only in C57BL/6 mice and were absent in BALB/c mice. The effects of GIZh-72 and diazepam in the marble burying test 2 h after ASS persisted in BALB/c but not C57BL/6 mice.

We have studied the impact of acute swimming stress on the behavioral and neurochemical effects of the pyrazole[c]pyridine derivative GIZh-72 (20 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). It was shown that anxiety-like behavior in open field test in BALB/c mice and marble burying test in C57BL/6 mice increased 1 hour after acute swimming stress. Decreasing of anxiety-like behavior in marble burying test was occurred in C57BL/6 mice and in open field test in both BALB/c and C57BL/6 mice 24 hours after acute stress. An increase of serotonin and a decrease of norepinephrine levels were registered in the hypothalamus in BALB/c and C57BL/6 mice, while an increase of norepinephrine, 3,4-dihydroxyphenylacetic acid levels and 3,4-dihydroxyphenylacetic acid/dopamine ratio were occurred in the prefrontal cortex in BALB/c. These changes correlated with increasing of anxiety-like behavior, but reversal of these neurochemical changes after treatment with GIZh-72 or diazepam or 24 hours after the stress was coincident with attenuation of anxiety-like behavior. Treatment with GIZh-72 or diazepam without the stress led to a decrease of anxiety-like behavior in open field test and marble burying test in BALB/c and C57BL/6 mice. The effects of GIZh-72 in open field test and marble burying test persisted, while the effects of diazepam in open field test persisted in C57BL/6 and increased in BALB/c mice 1 hour after the stress. Anxiolytic-like effect of GIZh-72 in open field test increased in BALB/c mice, but attenuated in C57BL/6 mice that accompanied the tendency to sedative effect 24 hours after the stress. Diazepam effects in open field test increased in C57BL/6, but absence in BALB/c mice 24 hours after the stress. The effects of GIZh-72 and diazepam in marble burying test persisted in C57BL/6, but not BALB/c mice 24 hours after the stress.

Abstract—We studied the dopamine-, serotonin-, and norepinephrinergic systems in various brain structures of BALB/c male mice on days 15, 42, and 64 of postnatal development (PND) in the model of autism spectrum disorder induced by sodium valproate administration (400 mg/kg, s/c) to pregnant females. It was found that the level of both catechol- and indolamines in the brain structures of control 15-day-old mice is considerably lower than in 64-day-old adult animals. Prenatal administration of sodium valproate (SV) caused a decrease in all parameters of monoaminergic neurotransmission in the striatum of mouse offspring aged 15 days but did not lead to neurochemical changes in other studied brain structures. By PND 42, the general pattern of changes in neurotransmitter concentrations did not differ from the developmental dynamics of neurotransmitter system maturation in the control group. The level of DA kept increasing and by PND 64, did not differ from controls. The parameters of serotonergic system changed similarly, with the peak serotonin concentration by PND 42 and a significant decrease by PND 64, whereas the level of 5-HIAA in the striatum increased gradually with maximum differences observed by PND 64. Thus, the data obtained suggest that administration of SV to pregnant females affects the activity of the dopamine- and serotonergic brain systems in the progeny, inducing its decrease in the striatum by PND 15 followed by recovery to control level by PND 64.

Изучены поведенческие и нейрохимические эффекты амитриптилина (10 мг/кг, внутрибрюшинно) и флуоксетина (20 мг/кг, внутрибрюшинно) после однократного и хронического введения в условиях моделирования хронического умеренного стресса у аутбредных мышей ICR (CD-1). После 28 дней воздействия стресса наблюдали усиление депрессивных реакций мышей в тесте «вынужденное плавание» и уменьшение уровней серотонина (5-НТ) и 5-оксииндолуксусной кислоты (5-ОИУК) в гиппокампе, повышение концентрации норадреналина (НА) в гипоталамусе. Однократное и хроническое введение амитриптилина или флуоксетина приводило к уменьшению времени иммобилизации и увеличению плавания мышей в тесте «вынужденное плавание». Антидепрессивный эффект флуоксетина, но не амитриптилина, после однократного введения сочетался с увеличением обмена 5-НТ в гиппокампе. Хроническое введение антидепрессантов приводило к повышению уровней НА в гипоталамусе. Таким образом, антидепрессивный эффект амитриптилина и флуоксетина может быть результатом усиления стресс-зависимых адаптивных механизмов, истощенных хроническим стрессом.

We studied the influence of intraperitoneal injection of ATP-sensitive potassium channels inhibitor glibenclamide in doses of 0.01, 0.1, 1, and 10 mg/kg on the effects of a new pyrazolo[C]pyridine derivative GIZh-72 (4,6-dimethyl-2-(4-chlorphenyl)-2,3-dihydro-1Hpyrazolo[ 4,3-C]pyridine-3-on, chloral hydrate; 20 mg/kg, intraperitoneally) in the marble burying and open-field tests in mice. It was found that glibenclamide produced an anxiolytic effect in the open-field test (in a dose of 0.01 mg/kg) and anticompulsive effect in the marble burying test (in doses of 1 and 10 mg/kg). The observed behavioral effects of glibenclamide did not depend on blood glucose level. At the same time, glibenclamide in subeffective (0.01 and 0.1 mg/kg) and effective (1 and 10 mg/kg) doses potentiated the psychotropic effects of GIZh-72 in these tests. It can be assumed that the psychotropic effects of GIZh-72 depend on functional activity of ATP-sensitive potassium channels.

The behavioral and neurochemical effects of amitriptyline (10 mg/kg, i.p.) and fluoxetine (20 mg/kg, i.p.) after single and chronic administration in the setting of unpredictable mild stress in outbred ICR (CD-1) mice were studied. After a 28-day exposure to stress, we observed an increase in depressive reaction in a forced swim test in mice, as well as reduced hippocampal levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and an increased hypothalamic level of noradrenaline (NA). Single and chronic administration of amitriptyline and fluoxetine shortened the immobility period and increased the time corresponding to active swimming in the forced swim test. The antidepressant-like effect of fluoxetine - but not of amitriptyline - after a single injection coincided with an increase in the 5-HT turnover in the hippocampus. Chronic administration of the antidepressants increased the hypothalamic levels of NA. Thus, the antidepressant-like effect of amitriptyline and fluoxetine may result from an enhancement of the stress-dependent adaptive mechanisms depleted by chronic stress.