Effect of Original Peptide Derivatives of Galantamine on Passive Avoidance in Mice.

The effect of original peptide derivatives of galantamine on scopolamine-induced memory impairment in mice was assessed using the passive avoidance test over 12 days. It was found that some galantamine derivatives administered in a dose of 1/20LD50 improved the memory in experimental mice, especially on days 5-12 of the experiment.

[Effect of 1,2,3,4-tetrahydroimidazo[4,5-c]pyridine and 1,2,3,4-tetrahydroisoquinoline derivatives on the behavior and the brain receptor system in rats].

Adducts obtained via the interaction of formaldehyde with histidine (1,2,3,4-tetrahydroimidazo[4, 5-c]pyridine-3-carboxylic acid (I)), tyrosine (7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (II)), and dopamine (6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (III)) influence the behavior and the state of the brain receptor system of rats upon chronic administration (10-day treatment at a daily dose of 50 mg/kg, i.p.). All the compounds studied decrease the horizontal and (to a lower extent) vertical motor activity and increase the quiescence period duration. On the other hand, the effects of compounds tested on the vegetative reactions were different: compounds I and III increased, whereas compound II decreased these reactions. Using the radioligand binding method, it was established that the treatment with compound I led to a decrease in the density of benzodiazepine receptors (B max of [3H]-flunitrazepam was 78% of the control level) and to a significant (148%) increase in the density of specific binding sites for [3H]-spiperone (reflecting the total density of dopamine (D2) and serotonin (5-HT2) receptors. The chronic administration of compound III produced a reliable decrease (76% of the control level) only in the density of benzodiazepine receptors. None of the tested compounds influenced the affinity of receptors with respect to the radioactive ligands used.

[Increase of seizure threshold and resistance to stress in rats after immunization against fragment of diazepam-binding inhibitor]. / Povyshenie sudorozhnogo poroga i ustoichivosti krys k stressu posle immunizatsii k fragmentu diazepam-sviazyvaiushchego ingibitora.

White rats were immunized against fragment of diazepam-binding inhibitor octadecaneuropeptide (ODN) with conjugate ODN bovine serum albumin. This rats have reduced reactions of fear and anxiety in stress model of "open field" and in conflict Vogel test; their pain sensitivity ("tail flick" test) was lowered. The number and intensity of generalized seizure reactions after injection of pentylenetetrazole were decreased. The results show that active immunization to endogenous ODN has stress--protective and anti-seizure effects.

Long-term changes of striatal D-2 receptors in rats chronically exposed to morphine under aversive life conditions.

Chronic morphine treatment has been shown to cause the development of hyperreactivity of the dopamine system detected as the increased behavioral and biochemical responses to the action of specific dopamine agonists. Furthermore, inverted changes in animal behavioral reactivity to the stimulation of presynaptic, proposed D-2 receptors by apomorphine in a low dose was found in our previous study when morphine was chronically used in animals under conditions of restraint. To estimate the nature and proposed receptor mechanisms of changes found in behavioral reactivity due to chronic morphine administration in aversive life conditions at the level of highly sensitive D-2 receptors, the density and affinity of [3H] spiroperidol binding sites was studied in these animals two weeks after the last opiate administration. Increased density and affinity of D-2 receptors probably indicating their hypersensitivity was found in animals chronically exposed to two-hour restraint stress, while a significant decrease in density accompanied by increase in affinity of these receptors was typical to rats chronically exposed to morphine under conditions of restraint. The data are discussed in aspects of quantitative and qualitative changes in D-2 receptors, and their proposed mechanisms and functional significance in the mediation of modified organism's functional state due to chronic opiate administration in different environmental conditions.

[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.

[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.

[Independent benzodiazepine and beta-carboline binding sites in the brain of aggressive and anxious-defensive mice]. / Nezavisimye mesta sviazyvaniia benzodiazepinov i beta-karbolinov v golovnom mozge agressivnykh i trevozhno-zashchitnykh myshei.

Distribution of specific 3H-flunitrazepam and 3H-beta-carboline-3-carboxylate binding sites in the brain regions of aggressive and timid-defensive mice was investigated before and after subchronic injection of diazepam (5 mg/kg). The absence of differences between the affinity and concentration of 3H-flunitrazepam binding sites in diencephalon and brain cortex in aggressive and defensive mice may be explained by general benzodiazepine receptor reaction on isolation and agonistic interaction stress. Significant predominance of 3H-beta-carboline-3-carboxylate binding sites in the brain cortex, as compared to the concentration of 3H-flunitrazepam binding sites suggests the presence of specific binding sites for beta-carbolines, which have specific distribution in the brain.

[Apropos of possible paired comparison of receptor-binding parameters obtained in one experiment]. / K voprosu o vozmozhnostiakh parnogo sravneniia parametrov retseptornogo sviazyvaniia, poluchennykh v odnom éksperimente.

The possibility of statistical comparison of receptor-binding parameters obtained on pooled biological material has been analysed. It was concluded that such comparison was possible when the data were processed in Cornish-Bowden plot, even with out repeating analogous experiments. The advantages of this approach over other methods are discussed.

[Characteristics of opiate receptors in the brain and spinal cord of morphine tolerant mice]. / Izuchenie kharakteristik opiatnykh retseptorov golovnogo i spinnogo mozga myshei, tolerantnykh k morfinu.

The in vitro studies of 3H-morphine binding to synaptosomal brain and spinal cord membranes and the in vivo detection of pA2 values were carried out in mice. Both morphine-tolerant and intact animals were used. Morphine-tolerant mice showed no changes in specific binding and naloxone pA2 values. Desensitization of neural tissue is most likely to result from variation in translation from opiate receptors to subreceptor effector systems.

[Mechanism of the tranquilizing action of electron structural analogs of nicotinamide]. / Mekhanizm trankviliziruiushchego deistviia nekotorykh élektronno-strukturnykh analogov nikotinamida.

The interaction of nicotinamide and its electron structural analogs (NMF and AzN compounds) with central benzodiazepine receptor antagonist Ro 15-1788 and GABA-ergic system antagonist bicuculline were studied in a conflicting situation test. NMF and AzN behaved as the agonists of GABA-benzodiazepine receptor complex. Like in diazepam, the anxiolytic effects of benzodiazepines and nicotinamide was prevented by bicuculline and Ro 15-1788. The given compounds were shown to be more active, than nicotinamide.

[Interaction of piracetam with 3H-imipramine binding sites and the GAMA-benzodiazepine receptor complex of brain membranes]. / Vzaimodeistvie piratsetama s mestami spetsificheskogo sviazyvaniia 3H-imipramina i GAMK-benzodiazepinovym retseptornym kompleksom membran golovnogo mozga.

Piracetam at a concentration of 10(-6) M was shown to behave as a noncompetitive inhibitor of 3H-imipramine specific binding to rat brain membranes. At the same time piracetam failed to influence specific binding of 3H-mianserin to membranes of guinea-pig cerebellum, which is indicative of its inability to suppress histamine H1 receptors, a component of 3H-imipramine specific binding sites. At a concentration of 10(-4) M piracetam does not change specific binding of 3H-flunitrazepam to rat hippocampal membranes in the absence of GABA, but in the presence of 5 X 10(-5) M GABA, like atypical tranquilizer mebicar, acts as a competitor of 3H-flunitrasepam binding. Though Ro-15 1788 did not suppress anxyolytic piracetam (and mebicar) effect, our results give evidence of a possible involvement of GABA-benzodiazepine supramolecular complex in the anxiolytic activity of piracetam.

[Effect of chronic psychogenic stress on a number of behavioral and neurochemical characteristics of rats]. / Vliianie khronicheskogo psikhogennogo stressa na riad povedencheskikh i neirokhimicheskikh kharakteristik krys.

Fifteen-day chronic stress with randomized footshock reinforcement (group 4) causes profound steady disturbances in the animal behavior. With the use of regular aversive reinforcement in the shuttle-box the rats were divided into two groups: "escaping" (group 2) and "non-escaping" (group 3). Minor behavioral disturbances were observed in group 2, moderate in group 3 and maximum in group 4. In the latter group "down-regulation" of beta-adrenoceptors and benzodiazepine receptors was observed. The receptor changes appear to be rather the result of psychogenic factors caused by randomized reinforcement than of physical stress as such.

[Effect of chronic psychogenic stress on the characteristics of synaptic membrane receptors in the rat brain]. / Vliianie khronicheskogo psikhogennogo stressa na kharakteristiki nekotorykh retseptorov sinapticheskikh membran golovnogo mozga krys.

It has been shown that the 15-day stressing of rats by means of stochastic footshock combined with light flashes leads to a relatively stable "behavioral depression". Twenty-four hours after the last exposure to stress crude synaptosomes isolated from the whole brain demonstrated an increase in the KD of 3H-dihydroalprenolol specific binding and a lowering of the Bmax of 3H-WB-4101 specific binding sites. Specific binding of 3H-flunitrazepam changes inconclusively: the decrease in the KD is followed by a reduction in the concentration of receptors. Specific binding of 3H-imipramine by brain membranes remains unchanged under the above conditions.

[Effect of leu-enkephalin and the delta-sleep-inducing peptide, M (DSIP), on endogenous noradrenaline release by brain synaptosomes in the rat]. / Izuchenie vliianiia lei-énkefalina i "peptida, indutsiruiushchego del'ta-son", M (DSIP), na vysvobozhdenie éndogennogo noradrenalina sinaptosomami golovnogo mozga krysy.

Fluorometry was employed to measure the noradrenaline (NA) content in rat brain synaptosomes depending on the duration of incubation, depolarization effects (40 mM KCl or 1.5 mM ouabain), composition of the synaptosomal fraction and concentration of the peptides. The 10-minute incubation in a potassium medium of a suspension of light synaptosomes was used as an optimal test-system for studying the peptide action. Leu-enkephalin inhibited the depolarization-induced NA release. The effect was abolished by naloxone. The delta-sleep-inducing peptide (DSIP) did not influence the neurotransmitter release at concentrations of 10(-8)-10(-5) M. A mixture of amino acids imitating the amino acid composition of the DSIP influenced spontaneous release of NA. This effect is discussed in connection with the physiological action of the peptide on its intraventricular injection.

[Effect of the chronic use of propranolol on the specific binding of 3H-WB-4101 with the membranes of the mesenteric vessels in rats]. / Vliianie khronicheskogo primeneniia proprapolola na spetsificheskoe sviazyvanie 3H-WB-4101 s membranami bryzheechnykh sosudov krys.

It has been shown that the 15-bay use of dl-propranolol (100 mg/kg a day) leads to a significant increase in the dissociation constant (CD) of the sites of specific binding of 3H-WB-4101 with membranes of rat mesenteric vessels. The concentration (Bmax) of the binding sites does not significantly change. Propranolol and other adrenoblockers do not possess any affinity for alpha-adrenoreceptors of rat brain synaptic membranes, i.e. changes in the properties of these receptors in vascular membranes cannot be accounted for by the direct action of propranolol in vivo or by the influence of the drug left in the membranes in vitro. It is concluded that desensitization of alpha1-adrenoreceptors of the peripheral vessels may be an essential element in the mechanism of the hypotensive action under the chronic use of beta-adrenoblockers.

[Behavioral and radioreceptor analysis of viloxazine stereoisomers]. / Povedencheskii i radioprotektornyi analiz stereoizomerov viloksazina.

The differences in the pharmacological effects of R(+)- and S(-)-isomers of the atypical antidepressant viloxazin were discovered in two behavioral models. The S(-)-isomer appeared 5 times as active as the R(+)-isomer under acute administration. In chronic administration, (15 days), the R(+)-isomer appeared ineffective. Comparison of the affinity of the racemate, R(+) and S(-)-isomers for alpha 1-, alpha 2- and beta-adrenoreceptors, as well as for serotonin, C1, benzodiazepine, imipramine and dopamine receptors did not demonstrate any stereospecificity of viloxazin isomers. It is assumed that some other receptors (histamine, acetylcholine) present the targets for the pharmacological action of viloxazin or the latter one has, like zimelidin , specific binding sites of its own.

[Effect of chronic administration of antidepressants on the binding of 3H-imipramine with mouse brain synaptic membranes]. / Vliianie khronicheskogo vvedeniia antidepressantov na sviazyvanie 3H-imipramina s sinapticheskimi membranami golovnogo mozga myshi.

Subchronic (14 days) administration of chlorimipramine and zimelidine, and a new morpholine derivative produces different effects on 3H-imipramine binding with synaptic membranes of the mouse brain. Chlorimipramine increases the concentration of the binding sites (Bmax), zimelidine raises both the Bmax and the dissociation constant, while the new morpholine derivative does not significantly change these characteristics. It has been demonstrated that the changes in the Bmax that occur during prolonged administration of chlorimipramine depend on the method for the obtaining of membrane brain preparations.

[Effect of chronic use of antidepressants on the state of benzodiazepine receptors in the mouse brain]. / Vliianie khronicheskogo primeneniia antidepressantov na sostoianie benzodiazepinovykh retseptorov golovnogo mozga myshi.

A study was made of the effect of a two-week administration of chlorimipramine, zimelidine and a morpholine derivative on benzodiazepine receptors of the mouse brain. The animals which received antidepressants demonstrated a significant increase in the binding sites of 3H-flunitrazepam without any changes in the dissociation constant as compared to control. The data on the evoked aggressiveness and latency of tonic corasole convulsions in the antidepressant-treated animals support the functional importance of the discovered changes in benzodiazepine receptors.

Content of DSIP, enkephalins and ACTH in some tissues of active and hibernating ground squirrels (Citellus suslicus).

Seasonal changes in the amount of DSIP-like material have been measured in extracts from the brain of Citellus suslicus. 2. Analysis of extracts from the brain of deeply sleeping ground squirrels shows that the level of enkephalin-like material reliably increases while that of ACTH-like material decreases. 3. It is concluded that the opiate brain activation system is among the factors participating in the induction of hibernation in ground squirrels.