[Electrophysiological study of the effects of topiramate on neocortical neurons in rats].

The effect of topiramate (topamax) on the electrical activity of frontal cortical neurons of neoencephalon was studied by microelectrode techniques in rats. Topiramate upon acute intraperitoneal administration and microionophoretic application dose-dependently reduced the frequency of spike activity within 17 - 30 min after injection at a dose of 40 and 80 mg/kg. At the same time, the agent did not change the membrane rest potential, and the magnitude and form of action potentials. Microionophoretically applied topiramate decreased the excitatory response to electroosmotically applied ethanol at "small doses" (ejected current < 50 nA) and enhanced the neuronal depression induced by ethanol at "large doses" (ejected current > 50 nA). It is suggested that the attenuation of alcohol seeking behavior observed after topiramate administration is due to suppression of ethanol activating effects in neoencephalon neurons, while the alleviation of alcohol withdrawal is associated with the central depressant activity.

Effects of naltrexone on firing activity of rat cortex neurons and its interactions with ethanol.

Naltrexone dose-dependently decreased neuron firing rate in the rat frontal cortex after intravenous (1-20 mg/kg) and microelectrophoretic administration. Microelectrophoretic applications of naltrexone reduced the excitatory neuronal response of neurons to low doses of ethanol (electroosmotic application) and potentiated depression of firing activity induced by ethanol in high doses. We concluded that opioid peptides take part in generation of spontaneous neuronal activity in the frontal cortex and neuronal excitation caused by ethanol in low doses. Naltrexone acts as a synergist of ethanol in its depressive effect on cortical neurons.

[Electrophysiological study of acamprosate effects on frontal cortical neurons in rats].

The effect of drug for alcoholism treatment acamprosate (campral) on spontaneous electrical activity of frontal cortical neurons was studied in rats. Acamprosate after acute intraperitoneal administration (600 mg/kg) and microiontophoretic application reduced the frequency of spike activity in about 30 % of cells studied. The agent didn't change the magnitude and form of action potentials. Microiontophoretically applied acamprosate reduced the excitatory responses to ethanol electroosmotically applied to neurons at "small doses" (ejected current < 50 nA) and increased the value of neuronal depression induced by ethanol at the "large doses" (ejected current 50 nA). Effects of acamprosate were dose independent. It is suggested that acamprosate has no interaction with specific postsynaptic receptors and its action is determined by presynaptic mechanisms.

[Adaptive function of the brain and problems of hypoxia].

Based on the findings of various authors and own experimental data it was concluded that adaptive behaviour is regulated by changing in the level of spontaneous neuronal activity. Spontaneous firing is monitored by brain metabolic M-cholinergic reaction which increased the efficacy of dendritic propagation by mechanism of K+ membrane channels blockade. High energy demands of cholinergic process creates a threat to nerve cells survival in hypoxic conditions.

[Sleep deprivation effect upon spatial memory consolidation in rats after one-day learning in a Morris water maze].

The effect of sleep deprivation by 'carousel' method on spatial memory consolidation in a Morris water maze was studied in Wistar male rats after one-day learning (in accordance to a protocol by Frick et al., 2000). It was found that after fast 3-hr learning the memory trace retains during 24-hr. Twenty four hour sleep deprivation followed learning impaired consolidation of spatial memory. So the rat model of a one-day learning is suitable for the studying of neurophysiological mechanisms of sleep deprivation effects on spatial memory consolidation.

Multiparameter analysis of EEG in old wistar rats after bilateral carotid artery ligation.

We showed that 302 of 840 EEG parameters in old Wistar rats significantly change 3 h after bilateral carotid artery ligation. All animals (n=7) died 250+/-47 min after ligation. EEG power spectra had signs of suppression (increased d-activity, decreased t-activity, and increased low-frequency alpha-activity) or activation of CNS (decreased high-frequency alpha-activity and paroxysmal increase in beta-activity). The coherence, synchrony, and entropy of potentials were reduced in the majority of brain regions. This method and scheme of experiments are suitable for the search and study of anti-stroke drugs.

Emotionality and the temporospatial organization of instantaneous EEG potentials.

The characteristics of the temporospatial organization of cerebral cortical potentials at different levels of genetically determined emotionality were analyzed by constructing topograms of instantaneous EEG levels in the inbred rat strains MR and MNRA. Two parameters were calculated for each topogram: the total level and the similarity coefficient. Power spectra were calculated for the values and these were found to change in an oscillatory manner. Interstrain differences were found in the correlated changes in total levels and similarity coefficients, in the durations of changes in the total level, which were more marked than those of similarity coefficients, and the nature of interhemisphere asymmetry. In MR rats, the power spectra of both measures showed significant peaks with modes at 2.0, 6.5, and 9.0 Hz. In MNRA rats, peaks in the spectra of these measures both coincided (2.0 Hz) and differed (7.0 Hz in the spectrum of the total level and 3.0, 4.5, and 6.0 Hz in the spectrum of the similarity coefficient). These data suggest different types of functioning of the reticulothalamocortical and hippocampocortical systems in rats of these strains.

[Interaction of tropoxin and its molecular fragments tropan and 3,4,5-trimethoxybenzoate with serotonin receptors of cortical neurons in the rat brain (a microionophoretic study)].

The effects of the antimigraine drug tropoxin and its main molecular fragments - tropan and 3,4,5-trimetoxybenzoate (TMB) - on the serotonin sensitivity of postsynaptic neuronal membrane in rat brain sensorimotor area has been studied using a microionophoretic (MIP) technique. All the three substances significantly reduce the excitatory neuronal response to serotonin, which is manifested by an increase in the rate of the spontaneous action potentials. With respect to the antiserotonin effect, the substances can be arranged in the following order: tropoxin > tropan > TMB. The sum of the effects of tropan and TMB (for both simultaneous and separate action upon the target cells) was significantly lower than the effect of tropoxin in all doses (MIP currents). It is concluded that a pronounced antiserotonin effect of tropoxin is produced only provided that the entire molecular configuration is retained. Tropan and TMB, being tropoxin metabolites, are probably capable of prolonging the antimigraine action upon the decay of tropoxin in the organism. A relationship between the structure and action of serotonin receptor blockers of the tropan series is discussed.

[Multiparametric analysis of the effect of ethanol in various doses on EEG in rats]. / Vliianie étanola vrazlichykh dozakh na éég krys. Mnogoparametricheskii analiz.

Multiparametric EEG analysis (840 parameters) was performed for 24 points over the entire dorsal cerebral cortex in outbred rats intraperitoneally injected with ethanol in low (0.75 g/kg), medium (2.0 g/kg), and high subnarcotic (4.5 g/kg) doses. Acute intoxication with low ethanol doses led to an increase in the spectral power and coherence in the frequency band of the dominating theta-rhythm peak (5.75-7.25 Hz), which was indicative of activation of the septo-hippocampal system (with improvement of the related functions such as attention, memory, and exploratory activity). The coherence was also increased in several high-frequency bands of the EEG alpha- and beta-rhythm. Ethanol administered in medium and high doses produced a shift of the dominating theta-rhythm peak to lower frequencies (4.50-5.75 Hz), which was evidence of reduced activity of the septo-hippocampal system and the related CNS functions. These doses of ethanol significantly decreased the spectral power and coherence in most of the high-frequency bands of the EEG alpha- and beta-rhythm, which can be explained by reduced energy and synaptic activity of the cortex leading to impaired high brain functions and the development of somnolent and narcotic effects. Using special sets of reliably modified parameters and a special algorithm, it is possible to solve the inverse problem of identifying experiments (EEG fragments) corresponding to low, medium, and high doses of ethanol.

[Comparative analysis of EEG spatial organization in the rats with different level of genetically determinated anxiety under ethanol]. / Sravnitel'nyi analiz prostranstvennoi oprganizatsii EEG u krys s raznym urovnem geneticheski determinirovannoi trevozhnosti pri vozdeistvii étanola.

The pecularities of EEG changes in the rats with geneticaly different level of anxiety was studed after ethanol injection. The biopotentials spatial synchronization and entropy in the "high anxious" rats (strain MR) did not increase under low dose; on the contrary the above changes were characteristic for the rats without anxiety signs (strain MNRA). After injection of middle and high ethanol doses the "high anxious" rats as compared with "low anxious" ones had the "simplification" of reaction type--the increase of narrow frequency coherence (i.e. linear biopotentials relationship) and spectral power of theta-activity (5.75-7.25 Hz), which was combined with the decrease of nonlinear biopotential characteristics. This fact is interpreted as the predominance of subcortical mechanisms of the brain functional state regulation over cortical ones. The significant decrease of high frequency EEG components in "high anxious" rats takes place under more high ethanol doses, presumably reflecting the increase of the anxiolytic level of ethanol effect.

[Comparative electroencephalographic evaluation of anxiolytics afobazol and diazepam in MR and MNRA inbred rats with different anxiety levels]. / Sravnitel'naia élektroéntsefalograficheskaia otsenka anksiolitikov afobazola i diazepama na inbrednykh krysakh linii MR i MNRA s raznym urovnem trevozhnosti.

The effects of two anxiolytic drugs, diazepam (10 mg/kg, i.p.) and afobazole (20 mg/kg, i.p.) on the EEG features was studied in MR and MNRA rats with different emotionality and anxiety levels in order to reveal an EEG marker of the anxiolytic action. For this purpose, 840 EEG parameters from 24 neocortex sites were determined and analyzed. In MR (but not in MNRA) rats, both diazepam and afobazole decreased the number of EEG parameters reliably changed upon the emotional-pain stress related to the intraperitoneal injections of 0.9% NaCl. Afobazole increased the theta-rhythm power in the spectral band of 4.75-7.25 Hz in MR rats, and in the band of 4.75-5.75 Hz in MNRA rats. Diazepam did not change the theta activity in MR rats, while decreasing it in the band of 6.00-7.25 Hz for MNRA rats. In addition, diazepam increased the spectral power in a broad frequency range of alpha and beta rhythms (8.75-17.25 Hz) in the rats of both lines, while afobazole did not produce such action. Common effects include a decrease in the spectral power within a narrow frequency band (7.5-8.5 Hz) at the boundary between theta and alpha regions. It is suggested that the latter effect can be used as the EEG marker of the anxiolytic action. The biopotential coherency in this frequency band was reduced in MR and MNRA rats only under the action of afobazole. The possibility of EEG changes related to the side action of anxiolytics and expediency of using the EEG markers in rats with different emotionality levels are discussed.

[Effect of novel anxiolytic agent aphobazole on coherence of the brain biopotentials in MR and MNRA rats]. / Vliianie novogo anksiolitika afobazola na kogerentnost' biopotentsialov kory golovnogo mozga krys linii MR i NMRA.

Effect of the anxiolytic drugs afobazole, diazepam, and chlordiazepoxide on the cortical biopotential coherency was studied in MR and MNRA rats with increased and decreased level of emotionality, respectively. Afobazole increased a difference in the biopotential coherency between rats of the two lines in the range of EEG theta, alpha, and beta rhythms. In the subrange of dominating theta activity (6.00-7.25 Hz), this effect took place at the expense of reduced coherency in MNRA rats in the absence of changes in the MR line. Afobazole decreased the biopotential coherency in the alpha activity band (7.5-8.25 Hz) in the rats of both lines. This is indicative of the presence of a CNS-stimulating component in the pharmacological activity spectrum of afobazole. The expediency of using afobazole in patients with different levels of anxiety is discussed.

[Effect of a novel antimigraine preparation tropoxin on EEG of MR and MNRA rats]. / Vliianie novogo protivomigrenevogo preparata tropoksina na EEG krys linii MR i MNRA.

Effect of the new antimigraine drug tropoxin on the EEG profile was studied in MR and MNRA rats with genetically determined high and low levels of emotionality, respectively. In MR rats, tropoxin decreased the number of the bioelectric activity parameters changed by the stressor action (0.9% NaCl, i.p.). The drug reduced the spectral power in the EEG delta band, and increased that in the theta, beta-1, and beta-2 bands. This was evidence of the central stimulating action and the possible enhancement of the exploratory activity. In MNRA rats no changes in bioelectric activity were observed in the low-frequency delta and theta bands, while the spectral power in the beta-1, and beta-2 bands showed a decrease. It was concluded that a neural component is present in the mechanism of the tropoxin action, which may play an important part in the therapeutic effect of the new drug.

[Features of the stress reaction in rats with genetically-determined emotionality (from EEG indicators)]. / Osobennosti stress-reaktsii u krys s geneticheski determinirovannoi émotsional'nost'iu (po pokazateliam EEG).

The features of the EEG spatial organization in two rat strains, i.e., with expressed emotional reactions (Maudsley reactive, MR) and less reactive (Maudsley nonreactive, MNR) were compared in two stress situations: during exposure to the action of pain (P) (i.p. injection of 0.9% NaCl solution) and during 24-hour water deprivation (D). Multichannel EEG recording (24 derivations) and their multiparametric estimation (840 signs) made it possible to differentiate characteristic features of the EEG spatial organization in rats with initially increased emotional reactions and passive behavioral strategy during exposure to stress. In both stress-inducing conditions, an increase in crosscorrelation and coherence between cortical potentials in parallel with rise of the spectral power in the range of high-frequency theta and its drop in the range of EEG high-frequency band was observed in the MR rats. The MNR rats showed the opposite changes. Different reactivity of the ratio between the coherence and spectral power of potentials was observed in two strains of rats. This index characterizes the level of the information-energy component of the spatial organization of cortical potentials. It is suggested that different character of the EEG changes reflects the features of interhemispheric relations, information-energy processes, and cortical regulation of autonomic processes in the system of adaptive stress reactions at different levels of emotionality and behavioral strategy.

[Spatial organization of EEG in rats with genetically determined emotionality]. / Prostranstvennaia organizatsiia EEG pri geneticheski determinirovannoi émotsional'nosti u krys.

In order to study the possibility of EEG discrimination of genetically determined emotionality (increased propensity to emotional and stress reactions and anxiety) brain electrical activity was recorded in rats of two strains: Maudsley Reactive and Maudsley Nonreactive (24 derivations from the convexital skull surface were used). The program package "Synchro-EEG" was used for EEG processing. It was demonstrated that the two rat strains were significantly different in 120 EEG parameters of 840 ones analyzed. On the basis of 37 parameters, each rat was correctly recognized as belonging to the respective group with the error of 4.89%. The analysis of the detected signs allowed their classification to be performed in accordance with the peculiarities of the emotional and cognitive processes and the level of nonspecific activation. Specific forms of interaction between these components in the system of emotional reactions were revealed.

[EEG study of the anxiolytic effect of scopolamine]. / EEG-issledovanie anksioliticheskogo éffekta skopolamina.

Effect of the central M-cholinolytic scopolamine on spatial organization of the rat brain electrical activity was studied under conditions of high and low emotional-stress responses. The EEG changes were estimated by 840 parameters. A possibility of the EEG discrimination by means of interstrain differences in responses to scopolamine, was shown. A more obvious decrease in spectral power and potentials coherence was revealed in Maudsley Reactive rats (MR) as compared with the Maudsley Nonreactive rats (MNRA), in parieto-temporal and occipital areas of the right hemisphere, and the reverse interrelationship occurred in the anterior parts of the right and posterior parts of the left hemisphere. These findings suggest some specifics in the spatial distribution of the maximum scopolamine action foci depending on the initial emotional level. Changes occurring under the scopolamine effect in different EEG frequency bands are different in the MR and the MNRA rats. The findings are discussed in respect to the EEG indices of anxiolytic component of cholinergic regulation of the brain activity.

[The effect of scopolamine on the spatial organization of rat cortical potentials]. / Vliianie skopolamina na prostranstvennuiu organizatsiiu potenstialov kory golovnogo mozga krys.

The influence of scopolamine (1 mg/kg, i.p.) on the spatial organization of the neocortical electrical activity was studied in rats. A decrease in the spectral power and coherence of brain potentials in the range of the dominant theta-rhythm peak (6.00-7.25 Hz) and their increase in the adjacent low-frequency band were observed. Both indices were decreased in the wide beta band (19.00-30.00 Hz). The described changes took place over the whole areas of the right hemisphere and parieto-temporal region of the left hemisphere. The obtained results are discussed with respect to the role of the cholinergic brain system in the higher nervous activity.