Biomedical subjects
Publications and source records attributed to P D Shabanov.
Antiedematous activity of new thiazolo[5,4-b]indole derivatives containing a fragment of isothiourea and characterized by higher antihypoxic activity compared to known antihypoxants was studied on a model of toxic edema of the lungs in mice. Compounds exhibiting high activity on two models of hypoxia (hypobaric and hemic) better protected from lung edema than compounds active only in hypobaric hypoxia.
The rats were adapted to hypoxic hypoxia by intermittent training in a flow pressure chamber for 3 days. The course of bemithyl treatment (25 mg/kg intraperitoneally, 3 days) started immediately after the 1st day of training. Bemithyl potentiated the adaptive metabolic changes in rat brain induced by repeated hypoxic hypoxia, increased the individual resistance to hypoxia, and produced a long-lasting effect.
A mathematical model is developed, which predicts the maximum deviation of adenine nucleotide content from the normal and the period of its restoration in the brain of animals. This model diminishes labor expenditures and duration of experimental studies. Moreover, it significantly increases the accuracy and reliability of the data. This model can assess the efficiency of pharmacotherapy of craniocerebral trauma aftereffects.
Experiments on rats showed that the individual resistance of the body to acute hypoxia is of decisive importance in the early recovery period after mechanical craniocerebral trauma. I.p. administration of ethomersol (25 mg/kg) during the three days following trauma decreased behavioral impairments in rats with different levels of resistance to acute hypoxia, restored the structure of individual behavior, and prevented metabolic disturbances in the brain. The results led to the conclusion that the antioxidant ethomersol is effective in hypoxia due to craniocerebral trauma.
6-Hydroxydopamine, which induces selective degeneration of the dopaminergic system of the brain, was given intraamniotically to rats on days 13 and 17 of intrauterine development at a dose of 75 microg/fetus. Similar experiments were performed with 6-hydroxydopamine on days 4 and 10 of neonatal life. Rats were subsequently reared and motor and emotional (dopamine-dependent) types of behavior were studied in adulthood, addressing behavior in the open field test, rotatory behavior, anxiety in an elevated cross maze, a place-preference conditioned response, acquisition of the ability to differentiate new and old arms in a Y maze, aggressivity in the "foreigner-resident" test, and self-stimulation in a Skinner box. Prenatal exposure, to a lesser extent than postnatal exposure, initiated rotatory and stereotypical behavior, decreased the level of anxiety (fear) in the elevated maze, and reinforced the effects of phenamine in the conditioned place-preference test, impaired the differentiation of old and new Y-maze arms, impaired aggressivity in the "foreigner-resident" test, and impaired self-stimulation of the lateral hypothalamus. It is concluded that the early postnatal period of development is more sensitive to the action of this neurotoxin than the prenatal period. This is associated with the critical periods of the formation of the dopaminergic system during ontogenesis, which depend on synaptogenesis.
The article is dedicated to therapeutic efficacy of a combination of the antihypoxant bemithyl and the antidepressant pyrazidol in patients with asthenoneurotic and asthenovegetative syndromes after moderate isolated brain injury (BI). The combined therapy was shown to reduce long-term sequences of BI such as asthenic symptoms, stabilize both lipid peroxidation processes and serum antioxidative systems.
Monotherapy of consequences of craniocerebral trauma with pyrazidol (1 mg/kg) produced an anxiolytic effect in animals highly resistant to hypoxia and activating effect on low resistant animals. Treatment with bemitil in a dose of 25 mg/kg produced a cerebroprotective effect and normalized individual behavioral characteristics, parameters of energy metabolism, and state of the antioxidant system in the brain of highly and low resistant rats. The effect of bemitil was most pronounced in highly resistant animals. During combined treatment, pyrazidol and bemitil had an additive effect in animals of both groups. They normalized behavioral reactions and prevented the development of metabolic disturbances in the brain.
In vivo microdialysis was used to study the effects of substance P on dopamine, dihydroxyphenylacetic acid, and homovanillic acid levels in the nucleus accumbens in rats. Each animal received sequential injections of physiological saline, 0.1 microg of substance P, and 1 microg of substance P into the lateral ventricle over three days. Dialysates showed increases in dopamine levels in response to neuropeptide, by 41% for the 0.1 microg dose and 71% for the 1 microg dose. The dynamics of these changes also depended on the concentration of the agent. Administration of 1 microg of substance P gave a peak dopamine level at 50 min; the neurotransmitter level remained significantly elevated 75 min after dosage with substance P. The dopamine level was increased only at 75 min when the 0.1 microg dose of neuropeptide was used. Changes in metabolite levels were also dose-dependent. After the 1 microg dose, the dihydroxyphenylacetic acid level increased by 28%, while the 0.1 microg dose produced no significant change in the level of this metabolite. The homovanillic acid level did not respond to administration of substance P at either dose. These data support the suggestion that the influence of substance P on the internal compensation system is to a significant extent mediated by dopaminergic mechanisms and provides a possible explanation for the effects of the neuropeptide seen in a conditioned place preference reflex.
The conditioned reinforcement properties of the synthetic glucocorticoid dexamethasone and the possible mechanisms of its action were studied using a conditioned place preference response. On test day 1, male Wistar rats were placed in a two-chamber apparatus and the time spent in each sector was measured for 10 min. Over the next six days, combinations of one of the chambers with administration of agents (reinforcement) were presented using injections of dexamethasone in one sector and injections of physiological saline in the other sector on alternate days. After combinations of dexamethasone (0.25-0.77 mg/kg, i.p.) with the non-preferred sector, rats showed dose-dependent place preference on test day 2; however, when dexamethasone was combined with the initially preferred sector, animals given dexamethasone at a dose of 0.75 mg/kg showed only a slight level of place avoidance. Subthreshold doses of phenamine (0.25 mg/kg) given alone had no effect; however, when given on a background of dexamethasone (0.25 mg/kg), phenamine evoked a place preference response in rats lacking an initial place preference for one sector. Administration of dexamethasone alone (0.25 mg/kg) in these conditions did not induce place preference. Administration of the dopamine D2 receptor antagonist sulpiride (20 mg/kg) 30 min before combinations of dexamethasone (0.25 mg/kg) with the non-preferred sector completely prevented the acquisition of place preference. Administration of the D1 dopamine receptor antagonist SCH23390 (0.05 mg/kg) had no effect on the acquisition of conditioned preference. These results provide evidence for the involvement of D2 receptors in conditioned place preference induced by dexamethasone.
Action of substance P on the contents of dopamine, dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens of rats was investigated with microdialysis procedure. During 3 days, each animal daily received i.v. the saline (the 1st day), 0.1 mcg of substance P (the 2nd day), 1 mcg of substance P (the 3rd day). Elevation of accumbal dopamine was observed amounting up to 41% and 71% for 0.1 mcg and 1 mcg of substance P, resp. Rates and duration of these changes also depended on neuropeptide concentration. 1 mcg of substance P produced the dopamine elevation with a peak by the 50th min. Moreover, in 75 min. after infusion of the neuropeptide, the levels of dopamine still remained increased. Response of metabolites also proved to be dose-related. With 1 mcg of substance P, the contents of dihydroxyphenylacetic acid increased by 28%, while with 0.1 mcg of substance P, this parameter did not change. Contents of homovanillie acid was unaffected by central substance P at the above doses. The data obtained corroborate the assumption of influence of the substance P on the reward system arising from its dopaminergic properties and provide a possible explanation of the neuropeptide effects observed in the conditioned place preference paradigm.
6-Hydroxydopamine (75 mkg), producing selective degeneration of dopaminergic neurons in the brain, was injected intraamniotically to every rat fetus on 13th or 17th day of mother pregnancy. The other experiment was performed, when 6-hydroxydopamine administered i.p. to newborn rats on 4th or 10th day of life. All rats were growing, and several dopamine-dependent behaviors were investigated in adult animals: open field, rotation behavior, anxiety in elevated plus maze, conditioned placed preference, differentiation of novel and known alleys of Y-maze, aggressive behavior in intruder-resident test, selfs-stimulation of lateral hypothalamus. Prenatal administration of 6-hydroxydopamine initiated rotations and stereotypy, decreased anxiety in elevated maze, reduced reinforcing properties of amphetamine in place preference test, disturbed differentiation of novel and known alley in Y-maze, high aggression and decreased self-stimulation in less degree that postnatal injection of neurotoxin. Therefore, the early postnatal period is more sensitive to neurotoxin action than prenatal period of development. This phenomenon is connected with critical periods of development of dopaminergic system in ontogeny.
In rats, the individual sensitivity to hypoxia plays an prominent role for recovery of animals after mechanic brain injury. Enthomerzol (25 mg/kg intraperitoneally) for three days after brain injury decreased behavioral disorders in rats with different resistance to acute hypoxia, recovered structure of individual behavior, prevented metabolic disorders in brain. Therefore, antihypoxant ethomerzol is effective as a drug against hypoxia due to brain injury.
Following the conditioning with dexamethasone, a dose-dependent place preference in non-preferred compartment was observed on the second test day in male Wistar rats. Amphetamine in subthreshold dose exerted no effect if administered alone and induced a place preference in an unbiased paradigm after pre-treatment with dexamethasone. Administration of D2-dopamine receptors' antagonist sulpiride 30 min prior to dexamethasone conditioning completely blocked the acquisition of the place preference. The D1-dopamine receptors' antagonist SCH23390 exerted no effect on the place conditioning. The findings suggest that the D2-dopamine receptors take part in conditioned place preference with dexamethasone.
Heating humans up to rectal temperature 39.0-39.5 degrees C induces a heat stress and a physiological adaptation. Blood cells were found to produce nitric oxide under these conditions, neutrophiles playing a major role in the process. In our opinion, the HSC 70 takes part in the process of the long cell adaptation augmenting the cells' functional activity. Hyperthermia leads to a massive temporal HSP 72 expression in the blood mononuclears. This expression seems to be due to alterations in the cellular proteins and to oxidative stress.
Modern concepts of neurophysiological mechanisms of the brain reinforcing systems are reviewed from A.A. Ukhtomsky's concept of dominanta. The brain mesocorticolimbic system was shown to play a key role in functioning of the brain reinforcing systems. Morphological and neurochemical organisation of this system determining the emotional sphere, was studied. The dopamine system was found to be the main neurochemical tool of the mesocorticolimbic system. Other transmitters, neuromodulators, and hormones play a regulatory role in the latter. The data obtained corroborate the authors' concept of fluctuating emotional gradient.
Explore the source record for details and available documents.
Effects of alaptide on self-stimulation of the lateral hypothalamus, rotation behaviour and learning ability were studied in rats growing either in social adaptation or in groups. The effects on self-stimulation were opposite in these rats. Alaptide facilitated the learning process in grouped rats and potentiated the indirect dophamine-mimetic action of amphetamine in isolated rats.
Amphetamine (1 mg/kg) promoted a pedal self-stimulation of lateral hypothalamus of Wistar rats in the Skinner box. An unipolar lesion of medical prefrontal cortex with kainic acid 10-14 days prior to an experiment did not prevent the facilitating effect of amphetamine on self-stimulation, though the levels of hypothalamic noradrenaline and dopamine are 43% and 4.5-fold decreased respectively, the hypothalamic serotonin concentration not changing. Lysergic acid diethylamid (10 mkg/kg) did not influence on self-stimulation response in rats with damaged medial prefrontal cortex, but after preliminary administration prevented the stimulating effect of amphetamine on self-stimulation of lateral hypothalamus. The data are discussed from the point of view of a hypothesis that the phenomenon obtained is associated with the presence of a hypothalamic autoregulatory dopaminergic system providing the realization of self-stimulation. However, it does not exclude that the modulating influence of medial prefrontal cortex on lateral hypothalamus is connected with not only dopaminergic but with serotoninergic axons too.