[Effects of heptapeptide selank on the content of monoamines and their metabolites in the brain of BALB/C and C57Bl/6 mice: a comparative study].

The effect of heptapeptide selank on the content of neurotransmitter monoamines and its metabolites in the brain structures of BALB/C and C57Bl/6 line mice under conditions of the open-field test were studied. Significant interstrain differences in the content of norepinephrine (NE), dopamine (DA), serotonin (5-HT) as well as in the levels of their metabolites in hippocampus, hypothalamus, striatum and frontal cortex of C57Bl/6 and BALB/C mice were demonstrated. In particular, the content of 5-HT and its metabolite 5-oxyindolacetic acid (5-HIAA) in hippocampus of BALB/C mice (with passive stress response) was higher than in the same structure of C57Bl/6 (stress-susceptible) animals. The injection of selank (0.3 mg/kg) led to an increase in the NE level in the hypothalamus of both mice strains. At the same time, selank produced opposite effects on the content of DA metabolites: the concentrations of dioxyphenylacetic (DOPAC) and homovanillic (HVA) acids were found to increase in frontal cortex and hippocampus of C57Bl/6 mice, while the same parameters in BALB/C mice were demonstrated to decrease. Selank induced a decrease in 5-HT and 5-HIAA levels in the hippocampus of BALB/C mice, but did not affect these parameters in C57Bl/6 animals. The obtained results are indicative of selectivity of the anxiolytic effects of selank.

[The correlation between brain weight and behavior changes in response to ethanol administration in laboratory mice]. / Korreliatsiia vesa mozga i izmenenii povedeniia v otvet na vvedenie étanola u laboratornoi myshi.

The effects of ethanol injections on the F2 offspring of the cross between large-brain (LB) and small-brain (SB) mouse strains selected for high and low relative brain weights, respectively, have been studied. The parental strains have significantly differed in brain weight for many generations. The effects of ethanol (2.4 g/kg) have been compared in four subpopulations of mice that differ pairwise in brain weight. One pair of subpopulations has been isolated from the hybrid group and the other, from generation 22 of selection of the parental strains. The results of ANOVA have demonstrated that brain weight is related to the response to ethanol injections. The parameters of stereotyped behavior, which increased in after ethanol injections and reflected the decrease in exploratory activity) were different in mice with high and low relative brain weights. The pattern of behavioral changes after ethanol injections is the second (after increased learning ability) behavioral trait found to be correlated with brain weight.

[Rapid tolerance to ethanol and high voluntary alcohol consumption in mice selected for brain weight]. / Bystraia tolerantnost' k étalonu i dobrovol'noe potreblenie bol'shikh doz alkogolia u myshei, selektirovannykh po vesu mozga.

Mice of two strains selected for small and large brain weight (SB and LB, respectively) had free access to 10% alcohol and water within three months. At the end of this period, they consumed alcohol in daily dose of 6.9 +/- 0.9 and 7.5 +/- 0.8 g/kg, respectively. After a period of imposed three-day abstinence, the alcohol consumption by the mice of these strains increased by 68.6 and 49.3%, respectively. Exploratory behavior of independent groups of mice from these strains was studied in the closed cross-maze. The animals were injected with ethanol (2.4 g/kg, i.p.) or vehicle twice with a weekly interval. In SB mice, the first ethanol administration increased the total time of maze exploration and the number of stereotyped visits. The second ethanol administration did not increase the time of exploration but increased the number of stereotyped visits even to the greater extent. The latter indicates the development of rapid tolerance and sensitization of these behaviors to the drug, respectively. The ethanol administration inhibited exploratory patrolling behavior and defecations. In LB mice, both the first and second ethanol administrations increased the number of stereotyped visits and decreased the exploration time and the number of defecations. The results do not support the psychomotor stimulant hypothesis of alcohol addiction. It is proposed that SB and LB mice may serve as models for Cloninger's types 1 and 2 alcoholics and may be useful for investigation of neuropharmacological mechanisms of stimulatory and inhibitory effects of ethanol.

[The content of dynorphin, Met-enk-Arg6-Phe7 and substance P (1-11) in the brain of mice with different levels of ethanol consumption]. / Soderzhanie dinorfina, Met--enk--Arg6--Fen7 i substantsii P (1-11) v mozge myshei s razlichnym urovnem potrebleniia étanola.

The dynorphin A (1-17), Met-enkephalin-Arg6-Phe7 and substance P levels were determined by RIA following Sep-Pak separation in the striatum, hippocampus and spinal cord of three strains of mice (C57Bl10/D1, A/Sn, A. CA). The C57Bl10/D1 mice had high consumption of 10% ethanol at free choice schedule, whereas the A/Sn and A. CA mice had very low one. The Met-enkephalin-Arg6-Phe7 level was found to be decreased only in the spinal cord and striatum of C57Bl10/D1 mice. It is suggested that decreased synthesis or processing of the proenkephalin may at least partly determine the high level of ethanol consumption by this strain of mice.

[Effects of delta sleep-inducing peptide on electrophysiological parameters of sleep during alcohol withdrawal in rats]. / Vliianie peptida del'ta-sna na élektrofiziologicheskie parametry sna krys v period alkogol'noi abstinentsii.

In rats with the persistent alcohol motivation the electrophysiological sleep pattern was studied during ethanol intake, after 24 and 48 hours of alcohol withdrawal. It was established that during the voluntary ethanol intake rats may be divided into two groups: with comparative deficit (1st group) and comparative abundance (2nd group) of REM sleep. Alcohol withdrawal caused differential alterations of sleep-wakefulness cycle: in the 1st group of rats REM sleep was more suppressed while in the 2nd group--more increased in comparison to those during ethanol intake. In all animals the SWS depression, increase of awakenings, the aggravation of falling asleep and decrease of sleep depth were observed. DSIP (0.1 mg/kg, i.p. 1 hour before sleep recording) was found to regulate sleep disorders caused by ethanol withdrawal. It makes the neuropeptide possible to be recommended for ethanol withdrawal syndrome treatment in clinical practice.

[Effect of ethanol on the levels of dopamine and its metabolites in the brain of rats with different degree of sensitivity to stress]. / Vliianie étanola na uroven' dofamina i ego metabolitov v mozge krys s razlichnoi chuvstvitel'nost'iu k stressu.

It was shown, that content of dopamine and its metabolites (DOPAC and HVA) are the same in two groups of rats with different time of immobilization in forced swimming test. One group of low active (LA) animals experienced the immobilization more than 300s, other high active (HA) rats for less than 120 s. Ethanol (2 g/kg per oris) increased the level of DA in the striatum and medial prefrontal cortex only in LA rats and besides, the concentration of dopamine after ethanol administration was higher in the n. accumbens of LA rats, than in that of HA rats. The authors suggest that differences in dopamine content between LA and HA rats are connected with different levels of voluntary alcohol consumption. The opportunity to use both groups of HA and LA rats for developing models of pathogenic heterogeneity of alcoholism is discussed.

[Analysis of the mechanism of the stress-protective action of delta sleep-inducing peptide]. / Analiz mekhanizma stressprotektivnogo deistviia peptida, indutsiruiushchego delta-fazu sna.

By RIA there were studied the contents of corticosterone, ACTH, beta-endorphin and insulin in the blood plasma, met- and leu-enkephalin in different regions of the rat brain and in the adrenal glands after a 6-hour immobilization. The stress increased the content of corticosterone, ACTH, beta-endorphin, but not insulin in the blood plasma, and the levels of met-enkephalin in the adrenal glands, but decreased the met-enkephalin contents in the striatum. The injection of DSIP (0.1 mg/kg, i/p) blocked partly the elevation of corticosterone only. The authors propose, that stress-protective action of DSIP is realized with the involvements of the hypothalamo-pituitary-adrenal gland system.

[The effect of adenosine and beta-endorphin on the contractions of the vas deferens in rats with various durations of ethanol narcosis]. / Vliianie adenozina i beta-endorfina na sokrashcheniia semiavynosiashchego protoka krys s raznoi dlitel'nost'iu étanolovogo narkoza.

Action of ethanol on animals with different predisposition to alcohol consumption depended on the level of ethanol metabolism or sensitivity of nervous system to alcohol. There was studied the ethanol effects on contraction of rat vas deferens. Such an approach enables to distinguish the metabolic effects from action on nervous system. It was shown, that dose of ethanol, which inhibits the contraction of rat vas deferens of by 50% is the same in both groups of rats, but the ED50 of adenosin and beta-endorphin were 1.7 and 4.7 times lower for vas deferens of predisposed rats. It's possible to suggest the differences between two groups of rats to be connected with the effects of ethanol on purinergic and endorphinergic system, but not with ethanol itself.

[Effects of ethanol on the concentration of neuropeptides, ACTH and corticosterone during immobilization stress]. / Vliianie étanola na kontsentratsiiu neiropeptidov, AKTG i kortikosterona na fone immobilizatsionnogo stressa.

It was shown, that stress increased the level of ACTH, beta-endorphin and corticosterone in the blood plasma of the rat. Injection of ethanol (1 g/kg) decreased the level of ACTH, but increased the levels of beta-endorphin in the rat subjected to immobilization stress. The immobilization lowered the levels of met-enkephalin in the striatum and medulla oblongata, but increased the content of neuropeptide in the adrenal glands. The concentration of leu-enkephalin and DSIP remained unchanged following the stress. Ethanol reversed the action of immobilization on the level of met-enkephalin in the striatum, but increased the content of DSIP in the thalamus. These results indicate that ethanol modified the activity of pituitary-adrenal-axis during stress and probably the stress-protective action of ethanol partly performed with the involvement of DSIP.

[Effects of sodium oxybutyrate on the level of catecholamines and serotonin and monoamine oxidase activity in patients with alcoholism]. / Vliianie natriia oksibutirata na urovni katekholaminov, serotonina i aktivnost' monoaminoksidazy u bol'nykh alkogolizmom.

Sodium salt of gamma-hydroxybutyric acid (Na-GHB) was administered to 37 drug-free alcoholic men in placebo controlled study. The psychotropic effect was evaluated using psychometric scale of 4 ranges. Changes in plasma levels of epinephrine, norepinephrine, dopamine, serotonin and platelet MAO-B activity were assessed. The psychotropic effect was observed in 27 (76%) patients. The baseline of dopamine concentration was significantly correlated with the expression of psychotropic effect. Na-GHB decreased dopamine concentration in responders. The possible involvement of dopaminergic system in the realization of psychotropic effect of Na-GHB was discussed.

[Interaction of ethanol with opiate receptors]. / Osobennosti vzaimodeistviia étanola s opiatnymi retseptorami.

Addition of ethanol to rat brain homogenate containing opiate receptors inhibits at a concentration of 50 mM the stereospecific binding of 3H-naloxone at 37 degrees C but not at 0 degree C, with the ID50 being 462 mM under these conditions. The temperature-dependent inhibition of the ligand binding suggests that ethanol does not compete with naloxone for specific binding sites of opiate receptors and changes the structure of lipids in biological membranes. Scatchard's analysis has demonstrated that apart from a decrease in the number of highly affinity binding sites of 3H-naloxone, the total amount of the binding sites remains unchanged both in the presence and absence of ethanol and constitutes 453 and 549 fmol/mg protein. It is assumed that ethanol might interconvert highly and low-affinity binding sites. Analysis of the effect of ethanol on 3H-naloxone binding with opiate receptors contained by synaptic membranes obtained from animals with varying predisposition to voluntary alcoholization has shown that ethanol inhibits to a greater degree ligand binding with membranes obtained from rats predisposed to alcoholization. The possibility of the involvement of receptors in the biochemical mechanisms by which the initial alcoholic motivation is effected is under discussion.

[Characteristics of the benzodiazepine receptors in rats with different predispositions to the development of experimental alcoholism]. / Kharakteristika benzodiazepinovykh retseptorov u krys s razlichnoi predraspolozhennost'iu k razvitiiu éksperimental'nogo alkogolizma.

A study was made of the density and affinity of benzodiazepine receptors in the cortex of the cerebral hemispheres and hippocampus of rats with different predisposition to alcohol consumption. No differences were revealed in the parameters under study in animals with varying duration of ethanol anesthesia and in rats after voluntary consumption of ethanol for 3.5 and 10 months. In a state of abstinence rats with physical dependence manifested a dramatic decrease in the density and affinity of benzodiazepine receptors in the cortex of the cerebral hemispheres. No changes described were detected in the hippocampus. The role of benzodiazepine receptors in the development of abstinence is discussed.

[Changes in the cytochrome P-450 content of the liver of congenic resistant mouse strains during chronic alcoholization]. / Izmenenie soderzhaniia tsitokhroma P-450 v pecheni myshei kongennykh rezistentnykh linii v protsesse khronicheskoi alkogolizatsii.

Differences were found in the levels of alcohol consumption in two pairs of congenic resistant mice (BI0.RI07, BI0.RIII and A/Sn, A.SW). BI0.RI07 and A/Sn mice were characterized as "drinking" compared to their congenic resistant partners BI0.R and A.SW. The concentration of cytochrome P-450 in the animal liver was measured at different periods of alcoholization. Certain correlation was found between the time-course of hemoprotein changes and the levels of alcohol consumption. The contribution of the major histocompatibility mouse system (H-2) to the correlations found is discussed.

[Comparative evaluation of the biogenic amine level of the brain and the ethanol kinetics in the blood of inbred C57B1/6 and CBA mice]. / Sravnitel'naia otsenka urovnia biogennykh aminov golovnogo mozga i kinetiki étanola v krovi myshei inbrednykh linii C57B1/6 i CBA.

The kinetics of ethanol in blood and the levels of serotonin, noradrenaline, and dopamine in the cortex of cerebral hemispheres, hypothalamus, thalamus, and brain stem were studied in male C57C1/6 and CBA mice characterized by predisposition and non-predisposition to the development of experimental alcoholism. C57B1/6 mice characterized by predisposition to the development of experimental alcoholism demonstrated a high level of serotonin and noradrenaline in the hypothalamus and brain stem and high rate of ethanol elimination from the blood. CBA mice non-predisposed to the development of experimental alcoholism were characterized by a low level of serotonin and noradrenaline in the hypothalamus and brain stem and by low rate of ethanol elimination from blood.

[Effect of ethanol on the concentration of enkephalins in the brain of rats with different levels of alcoholic motivation]. / Vliianie étanola na kontsentratsiiu énkefalinov v golovnom mozge krys s razlichnym urovnem alkogol'noi motivatsii.

Radioimmunoassay was used to measure the content of leu- and met-enkephalins in white random-bred rats divided into groups according to the duration of ethanol anesthesia and the levels of 15% ethanol consumption under the conditions of free choice. The concentration of neuropeptides was determined in the cortex of the large hemispheres, striatum, thalamus, and medulla oblongata. The short-sleeping animals manifested elevated concentration of leu-enkephalin in the cortex and that of met-enkephalin in the striatum, medulla oblongata, and thalamus. Prolonged alcoholization under the conditions of free choice led, in the much-drinking animals, to decreased concentration of leu- and met-enkephalins in the striatum, thalamus and medulla oblongata and to increased concentration of leu-enkephalin in the cortex. The importance of leu- and met-enkephalins in the pathogenesis of chronic experimental alcoholism in rats with different alcoholic motivation is considered.

[Effect of one-time and chronic administration of ethanol on the concentration of beta-endorphin in the brain of rats with different alcoholic motivation]. / Vliianie odnokratnogo i khronicheskogo vvedeniia étanola na kontsentratsiiu beta-éndorfina v golovnom mozge krys s razlichnoi alkogol'noi motivatsiei.

The concentration of beta-endorphin was determined in the cortex of the large hemispheres, thalamus, striatum and medulla oblongata of rats with varying duration of ethanol anesthesia and after a single injection of ethanol (2.5 g/kg). The content of beta-endorphin was also measured in the brain of rats which preferred and rejected 15% ethanol during long-term (up to 10 months) alcoholization. The data obtained indicate that ethanol produces a specific effect on the endorphinergic system in different brain structures of animals predisposed to voluntary alcoholization. A possible involvement of the neuropeptide in the formation of alcohol tolerance and physical dependence is discussed.

[Level of delta sleep-inducing peptide (DSIP) in the brain of rats with different alcoholic motivation]. / Soderzhanie peptida, indutsiruiuschchego del'ta-son (DSIP), v mozge krys s razlichnym urovnem alkogol'noi motivatsii.

Radioimmunoassay was used to measure the content of delta-sleep-inducing peptide (DSIP) in random-bred albino rats divided into groups according to the duration of ethanol anesthesia and the levels of 15% ethanol consumption under free-choice conditions. The concentration of the neuropeptide was assayed in intact brain, in the cortex of large hemispheres, medulla oblongata, thalamus and striatum. The short-sleeping rats manifested a statistically significant lowering of the DSIP content in intact brain homogenates, in the cortex of large hemispheres and striatum. On the contrary, thirty minutes after a single intraperitoneal injection of ethanol in a dose of 1 g/kg the DSIP content in the medulla oblongata, thalamus and striatum was found to be increased. The raising of the ethanol dose up to 2.5 and 4.5 g/kg was followed by a less significant increase in the neuropeptide content. Prolonged chronic alcoholization under free-choice conditions led after 12 months to the reduced DSIP content in the medulla oblongata, thalamus and striatum. The importance of DSIP for the pathogenesis of experimental alcoholism using rats with different levels of alcoholic motivation is discussed.

[Major histocompatibility system of the mouse (H-2) and body reaction to ethanol]. / Glavnaia sistema gistosovmestimosti myshi (H-2) i reaktsiia organizma na étanol.

A study was made of the response to ethanol of 2 pairs of the congenic resistant (CR) mouse strains, B10.R107, B10.RIII and A/Sn, A.SW. Upon a single intraperitoneal injection of ethanol in a dose of 4 g/kg bw CR strains manifested pronounced ethanol narcosis, while doses of 1 and 2.5 g/kg produced marked locomotor reaction. As regards these tests B10.RIII and A.SW mice were more susceptible to alcohol while B10.R107 mice were more resistant. The changes in locomotor activity induced by ethanol were dose-dependent in all the strains under study. It was disclosed in the course of chronic alcoholization that B10.RIII and A.SW mice consume less amounts of 10% ethanol. Mouse susceptibility to a single ethanol injection recorded from the duration of alcoholic narcosis and locomotion was found to correlate negatively with the ethanol consumption rate. The participation of the H-2 system in the response to ethanol is discussed.