[Neurotransmitter changes in the rat brain under combined intoxication induced by alcohol and morphine]. / Neiromediatornye narusheniia v golovnom mozge krys pri ostroi kompleksnoi intoksikatsii étanolom i morfinom.

We investigated the levels of biogenic monoamines and their metabolites in the rat hypothalamus, midbrain and cerebellum in acute complex intoxication with morphine and alcohol. The distinctive features of neurotransmitter disorders in various parts of the rat brain under a single exposure to ethanol and morphine, as well as the differences between acute morphine-alcohol and alcohol-morphine intoxication were established. Complex intoxication with alcohol and morphine resulted in signs of dopamine consumption only in the hypothalamus, regardless of the order of alcohol and morphine administration. Under conditions of alcohol-morphine intoxication an increase in the level of metabolites of the serotonergic system was noted in the investigated parts of the brain. In the midbrain and cerebellum the manifestation of combined action of ethanol and morphine is mainly determined by the effect of the last of the administered substances. There are features of changes in the indices of the dopaminergic and serotonergic systems in these experimental conditions, confirmed by the processes of dopamine catabolism and a decrease in the norepinephrine and serotonin concentration in the hypothalamus, which are not observed under individual action of ethanol and morphine.

[Particularities of γ-aminobutyric acid metabolism in the liver of rats during different types of alcohol withdrawal].

Activities of GABA-catabolising enzymes and the contents of some amino acids have been studied in the liver of the rats with different types of alcohol cessation after its systemic administration. Intermittent alcohol intoxication was accompanied by activation of liver GABA catabolism in case of the lowest alcohol load. However ethanol in higher doses and prolongation of intermittent alcohol administration decreased GABA catabolism. It is suggested that the observed changes may reflect non-specific adaptation of hepatocytes to the excessive alcohol consumption and its further cessation.

[Correction of metabolic changes in rats with sporadic alcoholic intoxication].

Faltering alcoholic intoxication is accompanied by activation of processes of lipid peroxidation in blood and a liver, and also reduction of levels of a number of amino acids in tissue. Compositions of "Tavamin" and "Neyramin" used for correction show normalizing effect on a pool of free amino acids in a liver and skeletal muscles, and also a number of biochemical characteristics in blood.

Neurotransmitter mechanisms of morphine withdrawal syndrome.

Activity of the major neurotransmitter systems in the brainstem and cerebellum was studied in rats with morphine withdrawal syndrome. The most significant changes were found in the brainstem of animals by the 36th hour and 7 days after morphine withdrawal. Dysfunction was revealed in the dopaminergic, noradrenergic, and serotoninergic neurotransmitter systems. Changes in cerebellar neurotransmission were most pronounced by the end of the first week of morphine withdrawal syndrome and manifested in the prevalence of inhibitory processes.

[Metabolic correction of neurochemical disturbances in the striatum by the amino-acid-based drug tavamin on the experimental model of morphine abstinence syndrome].

We have studied the content of neuroactive amino acids in the striatum of rats under the conditions of development of the morphine abstinence syndrome, as well as the possibility of its metabolic correction by amino-acid-based drug tavamin. Peculiarities in the metabolism of glutamate, aspartate, glycine, GABA, and taurine in addicted rats and the effect of tavamin on the background of abstinence syndrome have been revealed.

[Free amino acid pool in rat blood plasma under different conditions of alcoholization and correction with L-NAME and L-arginine].

The features of disturbances of the free amino acid pool under conditions of alcoholization in different regimes and its correction with L-NAME and L-arginine have been studied in rats. The most pronounced dysbalance of free amino acid was observed in animals upon interrupted alcoholization. The treatment with L-NAME and L-arginine on the background of chronic and interrupted alcoholization was found to normalize most indices of the of free amino acid pool. However, only the treatment with L-arginine led to a decrease in the level of ammonium in the blood plasma.

[GABA metabolism and neuroactive amino acids in the rat brain in morphine withdrawal syndrome].

The changes in the neuroactive amino acid contents, GABA metabolism and TCA reactions have been studied in rat brain regions under experimental morphine withdrawal (MW). MW was developed by means of the cessation of morphine intraperitoneal injections 1 and 36 hours, 3 and 7 days after the course of morphine administration for 7 days. In cortex the significant increase in the contents of glutamate, glutamine, asparagine, and alanine was observed in remote terms of MW. In cerebellum MW led to the decrease in the levels of glutamine and asparagine and increase in glycine level, followed by the GABA-transaminase activation and the succinate dehydrogenase inhibition. In thalamus prolongation of MW caused to the further inhibition of the activities of the GABA-catabolising enzymes. The changes observed in the amino acids levels and the GABA shunt activity are likely to be explained by indirect adaptation of the brain regions differing in the opioid receptors contents to protracted morphine administration.

[Effect of chronic morphine treatment on free radical state].

The state of an enzymatic component of the antioxidant system, intencity of lipid peroxidation (LPO) in the liver, nitric oxide level in blood plasma were investigated in rats subjected to chronic morphine intoxication. Male Wistar rats were treated with introperitoneal injections of 1% morphine hydrochloride twice a day. The daily dose of morphine was gradually increased trom 10 mg/kg (1-2 days) to 20 mg/kg (3-4 days), and up to 40 mg/kg starting at the fifth day. The first group of animals (n=8) received morphine injections for 14 and 21 days. Chronic morphine treatment was accompanied by marked inhibition of the peroxide-utilizing antioxidants in liver. This creates favourable conditions for H2O2 toxicity. Howewer, low level of thiobarbituric acid reactive products suggests involvement of some scavenger, which inhibits hydrogen-peroxide induced free radical processes. In vitro experiments suggests that morphine may be involved into reduction of H2O2 level, whereas administration of morphine to rats may also employ nitric oxide as the scavenger of reactive oxygen species.

[Interrupted alcohol treatment and liver: free radical homeostasis, nitric oxide, adaptive mechanisms].

Alcohol administration can result in liver damage. Reactive oxygen species (ROS), nitric oxide (NO) and their interaction are crucial factors in this process. The aim of work was to investigate, free radical state and mechanisms of adaptation of the antioxidant system (AOS) to stress, caused by interrupted alcohol intake. Repeated cycles of alcoholization caused an imbalance between production and utilization of various ROS. This imbalance was due to impairments in the system superoxide dismutase/catalase. Nevertheless, in most experimental groups there was clear reduction of lipid peroxidation (LPO) products evaluated by thiobarbituric acid reactive substances. This might be attributed to the antioxidant effect of NO. However, there was an increased level of transaminases in blood plasma. After 28 days of this experimental scheme all the parameters studied normalized.

[Glucocorticosteroid status and free amino acid level in blood plasma of rats under increased tolerance to ethanol].

The data are presented on the effects of ethanol treatment (3.5 g/kg of a 25 % solution, singly, daily, intraperitoneally for 1, 4, 7, 10 days) on development of tolerance to ethanol as assessed by changes in ethanol-induced sleep, corticosterone level dynamics and free aminoacis content in rat blood plasma.

[Chronic morphine intoxication and metabolism of neuroactive amino acids in the rat brain].

The influence of chronic morphine intoxication (for 7, 14 and 21-days) has been studied on the contents of neuroactive amino acids (GABA, glutamate, glutamine, alanine, aspartate, glycine, taurine) and on the activities of their metabolizing enzymes (GABA-transaminase, succinic semialdehyde dehydrogenase, succinic dehydrogenase, alanine- and aspartate-aminotransferase) in the rat brain regions: cortex, brain stem and cerebellum. We detected the significant decrease of glutamate level and the enhancement of GABA and aspartate levels in cortex after long-term morphine administration. In brain stem the increase in the contents of GABA, glutamine and taurine was noted together with the tendency in attenuation of this effect when intoxication was prolonged. The dose-dependent enhancement in the levels of glutamate, aspartate and glycine was observed after longer courses of morphine administration. In cerebellum the 21-day morphine administration led to attenuation of the morphine-induced increase in the contents of GABA, glutamate, alanine and glycine.

[GABA metabolism and contents of neuroactive amino acids in rat brain after acute morphine administration].

The activities of GABA-catabolizing enzymes (GABA-transaminase and succinic semialdehyde dehydrogenase), succinate dehydrogenase, alanine and aspartate amino transferases, the contents of GABA, glutamate, glutamine, alanine, aspartate and glycine were studied in rat brain regions after acute morphine administration. Intraperitoneal (i.p.) administration of 10 mg/kg morphine increased the glutamate level and decreased GABA and glycine levels in cortex. This may explain an excitable effect of morphine. When the higher doses of morphine were administered (20 and 40 mg/kg, i.p.), the most pronounced changes in the amino acids tested were observed in brain stem, possibly because of higher density of opiate receptors there. Decrease in glutamate level in the brain stem was accompanied by accumulation of its metabolic precursors glutamine and aspartate and decrease of inhibitory amino acids (GABA, glycine) leves, when the dose of 40 mg/kg was used. The data obtained indicate a dose-dependent relationship between the parameters studied and behavioral action of morphine.

[Role of vitamins in metabolic correction of alcohol intoxication]. / Rol' vitaminov v metabolicheskoi korrektsii alkogol'noi intoksikatsii.

The status of some vitamins during chronic alcohol intoxication was considered. The efficacy and expediency of vitamin therapy in comprehensive treatment of alcoholism has been proved.

[Metabolism of neuroactive amino acids in the rat cerebral cortex during morphine intoxication]. / Osobennosti metabolizma neiroaktivnykh aminokislot v kore bol'shogo mozga krys pri intoksikatsii morfinom.

The effect of acute and chronic morphine intoxication on the content of aspartate, glutamate, glutamine, glycine, and GABA in rat brain was studied. Under the acute intoxication conditions, the most pronounced changes were observed for a morphine dose of 10 mg/kg (b.w.) and manifested by prevailing excitation processes in this part of CNS. On the contrary, the chronic introduction of morphine led to an increase in the content of inhibitory amino acids.

[The effect of saltwort, Salsola collina, on the phospholipid composition of different sections of the rat brain after ethanol administration and its withdrawal]. / Vliianie solianki kholmovoi na fosfolipidnyi sostav razlichnykh otdelov golovnogo mozga krys posle vvedeniia étanola i ego otmeny.

The authors studied the effect of saltwort alcohol extract (Salsola CK, 200 mg/kg given daily per os for 7 days) on the content of phospholipid fractions in the cerebral hemisphere cortex and brain stem of rats in moderate alcohol intoxication and when the administration of ethanol was stopped (3rd and 7th day). Significant disorders of the phospholipid composition in these brain structures occurred in administration of ethanol and when it was stopped. Administration of CK had no neuroprotective effect on the phospholipid fractions of the cortex of the cerebral hemispheres and brain stem. The possible mechanisms of the discovered changes are discussed.

[Effect of acute alcoholic and acetaldehyde poisoning on lipid metabolism in the rat liver]. / Vliianie ostroi alkogol'noi i atsetal'degidnoi intoksikatsii na metabolizm lipidov v pecheni krys.

Lipid metabolism in the liver of rats in acute alcohol (25% solution, intraperitoneally, 4 g/kg, 30 minutes) and acetaldehyde (5% solution, intraperitoneally, 0.266 g/kg, 30 minutes) intoxication has been studied. It has been revealed that with acute injection of ethanol into the livers of experimental animals the level of cholesterol is decreased, the content of triacylglycerols and phosphatidylethanolamine is increased. Analogous changes in the concentration of lipid fractions have been also revealed after injection of acetaldehyde.

[Changes in lipid metabolism with the use of alcohol deterrent preparations]. / Izmeneniia metabolizma lipidov pri primenenii protivoalkogol'nykh preparatov.

The available experimental and clinical data in the literature on the effect of antialcoholic drugs (disulfiram, cyanamide, pyrazol) on the lipid composition of tissues (blood serum, liver, brain) are systematized and generalized. Drugs used in the treatment of alcoholism were found to cause essential changes in the metabolism of lipid fractions. This indicates the necessity for recording the detected changes in lipid metabolism in pharmacotherapy of alcoholism.

[Metabolic disorders in drug addictions]. / Metabolicheskie narusheniia pri narkomaniiakh.

The metabolic disturbances caused by compulsory drug intake into animals and men were characterized. The probable mechanisms of these disturbances are discussed.