[The effect of gidazepam on the level of monoamines in the brain of BALB/c mice]. / Vliianie gidazepama na soderzhanie monoaminov v mozge myshei linii BALB/c.

The authors studied the content of norepinephrine, dopamine, serotonin, and their metabolites in the hypothalamus and striatum of BALB/c mice after injection of tranquilizers phenazepam (0.05 mg/kg) and hydazepam (1 mg/kg). The drugs differed in their effect on the monoamine content in the brain structures under study, which was evidence of the difference in the mechanisms of their action.

[The anxiolytic action of an analog of the endogenous peptide tuftsin on inbred mice with different phenotypes of the emotional stress reaction]. / Izuchenie protivotrevozhnogo deistviia analoga éndogennogo peptida taftsina na inbrednykh myshakh s razlichnym fenotipom émotsional'no-stressovoi reaktsii.

The anxiolytic effect of the synthetic analogue of the endogenous peptide tuftsin (Thr-Lys-Pro-Arg-Pro-Gly-Pro) was studied in inbred mice Balb/c (C) and C57B1/6 (B6) with different heritable types of emotional-stress reaction. In C strain with genetically high level of anxiety and "passive" type of behaviour under conditions of avoidable and unavoidable stress (open field, elevated plus-maze, light-dark chamber) the heptapeptide prevented manifestations of anxiety being administered intraperitoneally in a wide range of active doses (200-3000 mcg/kg). The drug did not change the behaviour of B6 mice with low level of anxiety and active type of emotional-stress reaction. The described effect is comparable with tranquilizing-activatory action of low doses of benzodiazepine tranquillizers, however, in contrast to the latter, the heptapeptide has no side inhibitory behavioural effects even in high doses. The heptapeptide may be considered as a promising new anxioselective drug without side inhibitory behavioural effects which are typical for benzodiazepine tranquillizers.

[The pharmacogenetic concept of the anxio-selective effect]. / Farmakogeneticheskaia kontseptsiia anksioselektivnogo éffekta.

Hereditary variations in the effects of benzodiazepine tranquilizers depending on the phenotype of an emotional stress reaction (ESR) are described. The membrane-receptor relationship showed differences between C57B1/6 with an "active" ESR phenotype and Balb/c with a "passive" ESR at the GABA benzodiazepine receptor complex level. The pharmacological results evidenced the selective anxiolytic properties of the novel drug aphobazole (2-[2-morpholyno)ethylthio]-5-ethoxybenzimidazole dihydrochloride) which produced an activating anxiolytic action in Balb/c mice whereas no behavioral changes were observed in C57B1/6 mice.

[The effect of 1,4-benzodiazepine derivatives on 35S-tert-butylbicyclophosphorothionate binding in the brain of inbred mice with differing emotional stress reactions]. / Vliianie proizvodnykh 1,4-benzodiazepina na sviazyvanie 35S-tert-butilbitsiklofosoforotionata v mozge inbrednykh myshei s razlichnoi émotsional'no-stressovoi reaktsiei.

The effect of alprazolam, cinazepam, and hydazepam on the binding of 35S-tert-butylbicyclophosphorothionate with the brain membranes of inbred Balb/c and C57B1/6 mice with a different type of emotional-stress reaction was studied. The displacement curve of 35S-TBPS bound with alprazolam and cinazepam was two-phase in character with different degree of inhibition in the nanomolar and micromolar areas. Hydazepam displaced the bound radioligand only in micromolar concentrations. Displacement of the bound radioligand in the brain membranes began with lower concentrations of the used benzodiazepins in Balb/c animals than in C57B1/6 animals. The emotional-stress effect led to shift of the displacement curves of the bound 35S-TBPS in the direction of higher acting concentrations of the benzodiazepins in the brain membranes of mice of both lines.

[An analysis of the ionic regulation of the specific binding of 3H-diazepam depending on the phenotype of the emotional stress reaction]. / Analiz ionnoi reguliatsii spetsificheskogo sviazyvaniia 3H-diazepama v zavisimosti ot fenotipa émotsional'no-stressovoi reaktsii.

It was shown that low NaCl concentrations (less than 50 mM) had more pronounced stimulatory effect on [3H]-diazepam ([3H]-DZ) binding in brain membranes of Balb/c (C) mice than in C57B1/6 (B6) mice. These interstrain differences disappeared after emotional stress in "open field" (OF) test. Low doses of diazepam (0.75 mg/kg) and hydazepam (1 mg/kg) induced anxiolytic effect in C mice and restored their normal [3H]-DZ binding level in the presence of NaCl. On the opposite, effects of the same doses of the benzodiazepines were not revealed either on the behavior in OF test or on stimulating properties of NaCl in B6 mice. Both benzodiazepines (10 mg/kg) induced similar behavior (sedative) and receptor (decrease of NaCl stimulating ability) in B6 and C mice. We made a conclusion that the ability of NaCl to increase [3H]-DZ binding is a physiological index which reflects hereditary differences in emotional-stress reactions and behavioral effects of benzodiazepine tranquillizers.

[The ionic regulation of the receptor binding of S35-tert-butylbicyclophosphorothionate by brain membranes in inbred mice with different emotional stress reactions]. / Ionnaia reguliatsiia retseptsii S35-tert-butilbitsiklofosforotionata membranami mozga inbrednykh myshei s razlichnoi émotsional'no-stressovoi reaktsiei.

Comparative study of effects of ionic concentrations on [35S]-TBPS binding was performed on brain membranes of inbred mice. It was shown that low concentrations of LiCl (less than 100 mM) were more stimulatory effective in Balb/c (C) mice than in C57Bl/6 (B6) mice. On the contrary, stimulatory activity of NaNO (less than 100 mM) was more pronounced in B6 mice. The revealed line of activity of cations (Li+ > K+ > Na+) and anions (Cl- > or = Br- > I-) makes it possible to doubt interpretation of the obtained data only as affinity of the ions to their channels. We suggest the role of ions as modifiers of surface charge of neuronal membrane, that may be the main cause of the revealed interstrain differences.

[Interactions of GABA and Cl ionophore-binding subunits of GABA-benzodiazepine receptor complex in the brain of inbred mice]. / Vzaimodeistvie GAMK i Cl ionofor-sviazyvaiushchikh uchastkov GAMK-benzodiazepinovogo retseptornogo kompleksa v mozge inbrednykh myshei.

The displacement curves of the effect of GABA on the S35-tert-butyl bicyclophosphorothionate binding to the brain membranes of inbred mice were analysed. It was revealed the lack of marked interstrain differences in dependent on the ionic force of incubation medium modification of IC50. After incomplete stimulation of Cl(-)-ionophore subunit (50 mM NaCl) reliable interstrain differences in the value of nHill were shown. Bicuculline in the same conditions prevented the inhibitory effect of GABA (10(-5) M). But submaximal concentrations of bicuculline (5 X 10(-6) M, 10(-6) M) stimulated the radioligand binding in the presence of GABA (10(-6) M). It was marked more expressed bicuculline stimulation effect on the membranes of C57Bl/6 mice, as compared to BALB/c mice.

[Role of Cl-ionophore subunit in the functioning of GABA-benzodiazepine receptors]. / Izuchenie roli Cl-ionofornogo uchastka v funktsionirovanii GAMK-benzodiazepinovogo retseptora.

The displacement curves of the effect of picrotoxin on the S35-tert-butyl bicyclophosphorothionate binding to the brain membranes of inbred mice C57Bl/6 and Balb/c were analysed. The marked interstrain differences between modifications of IC50 and nHill dependent on the ionic force of the incubation medium were revealed. After partial stimulation of the receptor in the presence of 50 mM concentration of NaCl, the susceptibility of the receptor to picrotoxin was higher in the membrane suspension of C57Bl/6 mice than of Balb/c. Full stimulation of the receptor by 200 mM concentration of NaCl resulted in disappearance of interstrain differences. The value of nHill of C57Bl/6 membrane receptors increased after the change of the concentration of NaCl in the incubation medium from 50 to 200 mM, while it was invariable to Balb/c mice. It was marked that modification of the parameters of the binding of the radioligand to the membranes of C57Bl/6 mice was more latent, than for Balb/c mice.

[Analysis of the specific 3H-diazepam binding in the brain of inbred mice with differing emotionality]. / Analiz spetsificheskogo sviazyvaniia 3H-diazepama v mozge inbrednykh myshei s razlichnoi émotsional'nost'iu.

The influence of sodium chloride and gamma-aminobutyric acid (GABA) on H3-diazepam binding in CNS membrane fraction were investigated in C57Bl/6, BALB/c mice and their F1 hybrids. The addition of GABA (1, 10 and 100 microM) elevated the level of radioligand binding with CNS membranes in all the inbred mice in similar manner. The higher stimulating effect of sodium chloride (50, 100 and 150 mM) on the H3-diazepam reception was found in BALB/c mice and F1 hybrids, as compared to C57Bl/6 mice. It has been suggested that membrane-dependent conformational reconstructions of supramolecular receptor complex are the cause of genetic differences in the regulation of H3-diazepam reception by Cl(-)-ionophore.

[Effect of fenazepam on the ACTH content of the blood plasma in inbred mice under stress exposure]. / Vliianie fenazepama na soderzhanie AKTG v plazme krovi inbredbykh myshei pri stressovykh vozdeistviiakh.

The influence of phenazepam on plasma ACTH level before and after exposure to stress in the "open field" test was investigated in C57BL/6, BALB/c and F1(C57BL/6 X BALB/c) mice. The differences in the dose-dependent drug effect on the hormone level between strains were studied. A correlation between ACTH level and a characteristic animal behaviour has been established for different strains.

[Effect of brain acid extract products in inbred mice on 3H-diazepam reception]. / Vliianie produktov kislotnogo ékstrakta mozga inbrednykh myshei na retseptsiiu 3H-diazepama.

The influence of brain acid extract products, isolated by high-performance liquid chromatography on H3-diazepam binding was investigated in synaptosomal membranes of C57BL/6 and BALB/c mice. Fractions with stimulatory and inhibitory activity were isolated. Quantitative and qualitative differences in the effects and structure of ACTH-immunoreactive peptide fractions under study were established.

[Analysis of the spectrum of ACTH-immunoreactive peptides in the brain of inbred mice]. / Analiz spektra AKTG-immunoreaktivnykh peptidov v mozge inbrednykh myshei.

The ACTH-immunoreactive peptides (IP) distribution in the acid extract of brain and plasma fractions of C57BL/6, BALB/c and F1 (C57BL/6 X BALB/c) mice was investigated. IP were isolated by high-performance liquid chromatography. Interstrain differences in the IP spectrum were found in intact mice and mice after exposure to stress in the "open-field" test.

[Genetic control of the ACTH content of mouse plasma]. / Nasledstvennyi kontrol' soderzhaniia AKTG v plazme krovi myshei.

The content of ACTH in blood plasma of C57BL/6, BALB/C, F1, F2, and F1 X BALB/C mice was measured before and after an open-field exposure to emotional stress. Differences in the initial content of hormone and its changes after stress were revealed as dependent on the animal line. A suggestion is made about monogenic control over the initial level of ACTH.

[Biochemical heterogeneity of mitochondria]. / K voprosu o biokhimicheskoi geterogennosti mitokhondrii.

Rat liver mitochondria were fractionated on the basis of their sedimentation coefficients in the gradient of ficoll. The fractions ("heavy", "middle" and "light" mitochondria) were heterogeneous with regard to the content of protein, DNA, cytochrome a + a3 and respiratory activity. Heterogeneity of mitochondria did not result from the damage or microsomal and lysosomal contamination. The biosynthesis of DNA, RNA and proteins in the different fractions of mitochondria was studied. In vivo incorporation of radioactive precursor into RNA was highest in the fractions of "middle" mitochondria, whereas in vitro the "heavy" mitochondria showed maximum activity in the synthesis of RNA. In vitro DNA synthes was maximum in the fractions of "heavy" mitochondria, protein synthesis in "heavy" and "light" mitochondria. Activity of the synthesis of RNA, DNA and proteins in vitro depends on the content of DNA and cytochrome a + a3 in the different fractions of mitochondria. It is supposed that heterogeneity of mitochondria may be connected with their biogenesis.