[Biochemical bases of ftorafur-potentiating effects of perfluorodecalin, inducer of cytochrome P-450 dependent microsomal monooxygenases]. / Biokhimicheskie osnovy ftorafurpotentsiruiushchikh éffektov perftordekalina induktora tsitokhrom P-450-zavisimykh mikrosomnykh monooksigenaz.

Activity of cytochrome P-450-dependent monooxygenase system is significantly lower in hepatoma H-2-73 and Lewis lung carcinoma-bearing mice as compared to that in control animals. An inhibition of the cytochrome P-450 system was observed after the injection of ftorafur. Treatment of the mice with perfluorodecalin markedly increased the antineoplastic activity of ftorafur determined by a loss of the leucocytes and of the weight hepatoma H-2-73- and Lewis lung carcinoma resistant to ftorafur alone.

[Binding of (3)-imipramine by platelets from spontaneously hypertensive, normotensive, and Wistar rats and their behavior in stressful situations]. / Sviazyvanie (3)-imipramina trombotsitami spontanno gipertenzivnykh, normotenzivnykh i krys linii vistar i ikh povendenie v stress-situatsiiakh.

Spontaneously hypertensive rats (SHR), when submitted to stress remained active during both avoidance (water escape task test) and nonavoidance (forced swimming test) stress-situations. Wistar rats responded to a depression of active behaviour in forced swimming test and difficulty at resolving of complicated problem in water escape task test. did not differ in the affinity but the number of binding sites of 3H-imipramine was greater in SHR. SHR rats had a smaller number of binding sites that Wistar ones.

[Tyrosine hydroxylase activity in two-dimensional monomolecular films]. / Aktivnost' tirozingidroksilazy v dvukhmernykh monomolekuliarnykh plenkakh.

The activity of a neurospecific enzyme of tyrosine hydroxylase (TH) in monomolecular films formed onto solid surface was studied. The data obtained show that the formation of two-dimensional films onto negative-charge surfaces by the Langmuir-Schafer technology does not lead to the inactivation of the enzyme. Neuroleptic trifluoperazine increased the activity of TH. Monomolecular films of TH may be used as a sensitive element of biosensors for primary monitoring of neuroleptic-like compounds.

[Effects of zixoryn on pharmacokinetics of antipyrine in intact and sensitized guinea pigs]. / Vliianie ziksorina na farmakokinetiku antipirina u intaktnykh i sensibilizirovannykh morskikh svinok.

The effect of zixoryn, a hepatic inductor of cytochrome P-450, on the pharmacokinetics of antipyrine in intact and sensibilized guinea-pigs was studied. It was found that sensibilization of albumin increased the half-time (T1/2), AUC and decreased the total body clearance (Clt) of antipyrine and the renal clearance (Clr) of metabolites in urine. The administration of zixoryn in sensibilized animals decreased T1/2 and AUC and increased the clearance of antipyrine and its metabolites.

[Study by the intracerebral microdialysis method of the effects of atypical neuroleptics and anxiolytics on striatal release and metabolism of dopamine in awake rats]. / Izuchenie metodom vnutrimozgovogo mikrodializa vliianiia atipichnykh neiroleptikov i anksiolitikov na vysvobozhdenie i metabolizm dofamina v striatume bodrstvuiushchikh krys.

Using brain microdialysis in awake rats effects of risperidone, ritanserin, buspirone, sulpiride and 5-methoxy-N,N-dimethyltryptamine (MeODMT) on striatal dopamine (DA) release and metabolism were studied. Risperidone, sulpiride and buspirone increased levels of DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Ritanserin failed to affect DA release, while increased DOPAC and HVA levels. MeODMT had no effect on striatal DA release and metabolism. Possible interaction between DA and serotonin systems is discussed.

[Selective inhibition of monoamine oxidase in bovine brain by befol and moclobemide]. / Ob izbiratel'nosti tormozheniia monoaksidazy mozga byka befolom i moklobemidom.

Effects of befol and moklobemide on thyramine-, serotonin- and 2-phenyl ethylamine deaminase activities of mitochondrial monoamine oxidase from bovine truncus cerebri were studied. These drugs are reversible noncompetitive inhibitors of the enzyme not requiring preincubation. They inhibited most effectively the serotonin deaminase activity as compared with phenyl ethylamine deaminase activity, however they should not be concerned with typical inhibitors of monoamine oxidases of the A type as inhibition of thyramine deaminase activity was not found.

[The action of befol and its derivatives on monoamine oxidase of different origins]. / Deistvie befola i ego proizvodnykh na monoaminoksidazu razlichnogo proiskhozhdeniia.

The effect on deamination of serotonine, dopamine, tiramine and 2-phenylamine of benzamide derivatives befol, moclobemide and LIS-641 was studied. Befol and moclobemide are inhibitors of serotonine deaminating activity of MAO. The different sensitivity of this activity to the effect of the benzamide derivatives in beef or rat brain and human placenta was noted. The inhibition was more distinct in tissue homogenate than in corresponding mitochondrial fractions.

[The effect of the deprivation of paradoxical sleep on the rotational and stereotyped behavior induced by selective agonists of the dopamine receptors]. / Effektivnost' deprivatsii paradoksal'noi fazy sna na rotatsionnoe i stereotipnoe povedenie, vyzvannoe selektivnymi agonistami dofaminovykh retseptorov.

The ability of selective D1 and D2 agonists of dopamine (DA) receptors SKE-38393 and Ly-171555 to induce rotational and stereotypes behaviour were studied in rats with unilateral striatal kainic acid lesion before and after procedure of REM sleep deprivation (REMSD) lasting for 5 days. It was found that REMSD SKF-38393 given along induced the ipsilateral rotation. REMSD increased the circling and decreased an oral stereotype simultaneously when SKF-38393 and Ly-171555 were given together. The depletion of brain DA in part with alpha-methyl-p-tyrosine (AMPT) in nondeprived rats fails to influence the rotational behaviour and stereotype when SKF 38393 was injected 30 min following Ly-171555. After REMSD the AMPT pretreatment prevents the rotational behaviour caused by Ly-171555 which restores SKF-38393. The results suggest that prolonged REMSD may induce nonidentical changes in the sensitivity of the postsynaptic D1 and D2 receptors.

[Effect of tuftsin and hydroxymethacil on tyrosine hydrolase of macrophages in chronic stress]. / Vliianie taftsina i oksimetatsila na tirozingidrolazu makrofagov pri khronicheskom stresse.

It has been established that rat peritoneal macrophages possess tyrosine hydroxylase activity which has been characterized by KM4, 2 microM, Vmax 30 nmole/min per mg of protein. After 15 days of electronociseptive stimulation almost all tyrosine hydroxylase activity has been established in the form which has tyrosine KM47.0 M and Vmax 18.6 nmole/min. per mg of protein. Immunostimulator hydroxymethacil++, at its intraperitoneal injections to stressed rats during 7 days induced the appearance of low-affinity form of tyrosine hydroxylase with KM270 microM and Vmax 27.8 nmole/min.per mg of protein. The same low affinity form of the enzyme has been established after injections of tuftsin which possesses immunostimulating properties.

[Dynamics of synaptosomal membranes in experimental neurosis in animals using donor-acceptor pairs of luminophores]. / Izuchenie dinamiki sinaptosomal'nykh membran pri éksperimental'noi nevrotizatsii zhivotnykh s ispol'zovaniem donorno--aktseptornykh par liuminoforov.

Dynamic of synaptosomal membrane's structural parameters (fluidity, protein clusterization, thickness of lipid bilayer) during chronic (15 days) psychogenic stress was compared with kinetic of membrane bound enzyme--Na,K-ATPase. For evaluation of structural changes in membranes a special multiprobe method, based on the use of fluorescent probes ANSA and pyrene, fluorescence of endogenous tryptophane and inductive-resonance energy transfer was designed. The data obtained indicates correlation between structural and functional changes in synaptosomal membranes. It was also concluded that the multiprobe procedure used is a sensitive and adequate tool for investigation of structural changes in biomembranes.

[Dependence of the effects of tripeptide MIF and lithium chloride on the degree of supersensitivity of dopamine receptors of the brain]. / Zavisimost' éffektov tripeptida MIF u litiia khlorida ot stepeni superchuvstvitel'nosti dofaminovykh retseptorov mozga.

The desensitizing effects of MIF and lithium in respect to supersensitive striatal DA receptors in rats with unilateral lesion of the nigro-striatal pathway by 6-hydroxydopamine were revealed. Two groups of 6-hydroxydopamine-denervated rats were selected by their qualitative responsiveness to apomorphine-induced rotational behavior. It was found, that MIF and lithium (subchronic administration) did not modify behavioral supersensitivity in the highly sensitive group which showed two-peak rotational pattern in response to 0.05 mg/kg apomorphine, which was converted into a single-peak rotational pattern by haloperidol. On the contrary, administration of MIF and lithium for 21 days inhibited the apomorphine-induced rotations to 54 and 65% respectively in the less supersensitive group, which showed a single peak rotational pattern to apomorphine. Moreover, haloperidol showed the high antagonistic potency in these animals. These results suggest, that MIF and lithium might not exert desensitizing effects in the presence of high degree of supersensitivity of the striatal DA receptors, which is probably involved, for example, in the phenomenon of persistent tardive dyskinesia.

[Post-stress correlation of the functional activity of macrophages by tuftsin and its derivatives]. / Poststressornaia korreliatsiia funktsional'noi aktivnosti makrofagov taftsinom i ego proizvodnymi.

The effect of 15 day programmed neurotization on the functional activity of the peritoneal macrophages has been studied. The NBT-test and the adhesion measurements were used. The experimental neurosis resulted in the decrease of the macrophage functional activity and in leukopenia. Tuftsin did not restore the stress induced depression of macrophage activity but led to additional rise of the adrenal glands weight and to pronounced granulocyte-monocytosis. Pentapeptide analog of tuftsin gave the additional inhibition of NBT-activity of the macrophage. Heptapeptide analog favoured the restoration of the macrophage activity after neurotization and stimulated lymphopoiesis.

[Effect of the N-terminal fragment of substance P1-4 on the somatic manifestations of the stress reaction and on the catecholamine content of the adrenals in rats]. / Vliianie N-terminal'nogo fragmenta substantsii P1-4 na somaticheskie proiavleniia stressovoi reaktsii i soderzhanie katekholaminov v nadpochechnikakh krys.

The antistress affect of the substance P1-4 N-terminal fragment (ARG-Pro-Lys-Pro, 100 mkg/kg, i.p.) has been studied on the model of immobilization stress in rats. It was ascertained that the preparation of protective effect is revealed to the greatest extent on the exhaustion stage (48 h of immobilization), which served to prevent the lymphoid organs mass reduction and ulcer development and also accounted for greater adrenaline and noradrenaline content preservation in tissues and chromaffin cells of adrenal glands in stressed animals.

[Effect of tuftsin and its analog on learning, memory and exploratory behavior in rats]. / Vliianie taftsina i ego analoga na obuchenie, pamiat' i issledovatel'skoe povedenie krys.

On Wistar male rats the influence of tetrapeptide tuftsin and its analogue TP-1 (300 mkg/kg, i/p) on animals behaviour was studied. It is shown that administration of peptides increases the rat's exploratory activity. Activating influence of TP-1 was continued for 6 h. Daily multiple administration of tuftsin or TP-1, 15 min prior to the beginning of experiments facilitates the learning and stability of conditioned reaction with food reinforcement. Experimental animals react significantly weaker than the control ones to emotionally negative influence, produced by a sharp reduction of the amount of alimentary reinforcement control.

[Characteristics of the action of psychostimulants on learning and memory in rats]. / Osobennosti deistviia nekotorykh psikhostimuliatorov na obuchenie i pamiat' krys.

The effects of intraperitoneal injections of psychostimulant drugs: centrophenoxine (50 mg/kg) and peptide analog of tuftsin TP-1 (300 micrograms/kg) on the processes of elaboration and retention of conditioned reflex have been experimentally studied. The animals were trained with food reward in 30 trials per day. Psychostimulant drugs or saline were injected after the 10th trial. The elaboration of conditioned reflex was continued 30 min later. The retention was tested 24 h, 7 and 30 days later. It was established that both drugs induce an increase in memory traces stability during 30 days. These findings provide direct evidence that psychostimulant drugs, centrophenoxine and peptide substance TP-1, when injected during consolidation phase can enhance memory storage processes.

[Effect of antidepressants on reverse neuromediator uptake by the synaptosomes in control and stressed rats]. / Vliianie antidepressantov na obratnyi zakhvat neiromediatorov sinaptosomami kontrol'nykh i stressirovannykh krys.

The influence of chemically different antidepressants on the uptake of 5-HT, dopamine and GABA by the rat brain synaptosomes was tested, using radioisotope technique in control and chronically stressed (14 days) animals. Drugs were more potent inhibitors of neurotransmitter uptake in synaptosomes of stressed animals, as compared to synaptosomes from control ones, the activity increasing proportionally to the changes in a particular uptake system. It is suggested that the drugs inhibit the uptake of neurotransmitters studied by changing the properties of synaptosomal membrane lipid bilayer. It is also evident that neurochemical properties of psychotropic drugs must be evaluated on the membranes from animals in the model of experimental psychopathology.

[Effect of aminazine and triftazin on the synaptosome membranes of the rat cerebral cortex]. / Vliianie aminazina i triftazina na sinaptosomnye membrany kory golovnogo mozga krys.

Fluorescent probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and pyrene were employed in studying the effect of aminazine and triftazin versus that of imipramine on microviscosity of rat brain cortex synaptosomal membranes. Unlike imipramine, the neuroleptics decrease microviscosity of membrane's lipid bilayer. All drugs decrease fluorescence of endogenous tryptophan, but fail to change fluorescence of L-tryptophan in the solution. It is concluded that neuroleptics induce conformational perturbations in membrane-bound proteins modifying microviscosity of lipid bilayer whereas imipramine changes the surface electric charge of lipid bilayer of synaptosomal membranes.

[Interaction of psychotropic preparations with the synaptic membranes of the cerebral cortex in rats]. / Vzaimodeistvie psikhotropnykh preparatov s sinapticheskimi membranamikory golovnogo mozga krys.

Interaction of psychotropic drugs with synaptosomal membranes from rat brain cortex was investigated by fluorescent probes. The data obtained indicate that all studied drugs change the state of membrane's surface. Tranquilizers, unlike antidepressants and neuroleptics, decreased fluorescence of the probe. Neuroleptics, unlike other drugs, penetrated deeper into the membranes hydrophobic core.

[Morphometric ultrastructural study of the adreno- and noradrenocytes of the rat adrenal during immobilization stress of varying duration]. / Morfometricheskoe ul'trastrukturnoe izuchenie adreno- i noradrenotsitov nadpochechnika krysy v usloviiakh immobilizatsionnogo stressa razlichnoi dlitel'nosti.

The ultrastructural organization of secretory granules, containing adrenaline (A) or noradrenaline (NA) was studied in chromaffin cells of the rat adrenal gland after 3-, 24- and 48-hour immobilization stress. Using cytochemical electron microscopic Tranzer's method and the method of morphometry, the number of normal dense cores, "empty" and "semiempty" vesicles was calculated. It was shown that the total content of vesicles and the ratio of investigated types of both adrenaline- and noradrenaline-accumulating granules were markedly changed during stress. The degree of such stress-induced reorganization depended on the stage of stress reaction and involved first A-cells and then NA-cells.