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The individual sensitivity of the male Wistar rats to acute pentylenetetrazole injection was studied, the density and the affinity of benzodiazepine receptors in the cerebellar cortex for 3H-diazepam was measured. It was demonstrated that the reactivity of benzodiazepine receptors underlies the individual sensitivity to pentylenetetrazole. The animals with higher sensitivity were characterized by more intensive reaction than the control and resistant animals, i.e., by an decrease in the receptors density (the initial receptors density being equal in the sensitive, resistant, and control animals). Daily injections of a subconvulsive dose of pentylenetetrazole during 24 days increase the animal sensitivity to this substance, and this was accompanied by an increase in the reactivity of benzodiasepine receptors. Later on, the produced high sensitivity became somewhat lower but persisted for 6 months. The receptors density in this period reduced almost by half. In sensitive rats, a single low dose of pentylenetetrazole injected 6 months after treatment increased the density of benzodiazepine receptors. The age-matched controls, the same acute dose of pentylenetetrazole decreased both the receptor density and affinity of their binding. It is suggested that the increase in reactivity of benzodiazepine receptors is actualized via the intracellular metabotropic feedback mechanism.

Typological behavior reactions of WAG/Rij rats were studied from the standpoint of divergent modulatory integration hypothesis. This rat strain has a genetically determined dominant dysfunction of the benzodiazepine system of the thalamic nuclei. This disorder provokes an epileptiform disease such as absence epilepsy. It was suggested that the dysfunction of this system would result in a modification of the modulatory systems, which support the motivation states of escape and avoidance reactions as well as of the modulatory systems, which form the emotional states. Modifications of these states are the background of typological behavioral features of WAG/Rij rats. It was shown that WAG/Rij have the lower threshold of the development of haloperidol catalepsy, higher levels of fear and depression. On the first day of training in a shuttle box, WAG/Rij rats demonstrated better avoidance performance than Wistar rats. On the second and 28th days, the amnestic effect of the epileptiform disease was observed. The amnestic effect was also observed after passive avoidance conditioning. The results are discussed in terms of the modulatory integratin hypothesis.

Convergent intercellular synaptic interaction is actualized, mainly, by two neurotransmitter systems: glutamate- and GABA-ergic (excitatory and inhibitory postsynaptic potentials, respectively). Fast and slow postsynaptic receptors of glutamate- and GABA-ergic synapses are described. All other brain systems are divergent neuromodulators. Modulators are released into the intercellular space and simultaneously interact with a large population of neurons. A hypothesis of divergent modulatory integration is described: the divergently functioning neuromodulators actualize stable functional states of the brain via appropriate long-term modification-inducing receptors. These stable states are a biochemical basis of the motivational and emotional states. Mechanisms of the secondary nuclear signaling triggered by the long-term modification-inducing receptors consolidate the stable states. The hypothesis of divergent modulatory integration is substantiated in the paper on the basis of the evidence obtained by the author and his collaborates. The haloperidol catalepsy and pentile-netetrazole kindling are considered as a behavioral model of the divergent modulatory integration. The experimental data suggest that divergently functioning neuromodulators actualize and consolidate general motivational and emotional states via the appropriate long-term modification-inducing receptors. The consolidation is structurally-specific. The motivational and emotional states concomitant of learning and memory are a specific variation of the general motivational and emotional state depending on the learning situation.

Neuromodulators and neurotransmitters systems of brain were demarcated on the basis of their feature. The neurotransmitters ability to EPSP and IPSP generation were used for their indication. The neuromodulators divergent morphological feature and their ability to induce a slow intracellular metabotrope reaction were used for their indication. In this review fast and slow glutamate and GABA postsynaptic receptors are discussed. Modulators are released in the intercellular space and interact with a large population of neurons. The hypothesis of a divergent modulatory integration suggests that neuromodulators, functioning divergently actualize stable functional states of the brain via their own long-term modification-inducing receptors. These stable states form the biochemical basis of motivation and emotional states. The secondary nuclear signal mechanisms triggered by the long-term modification-inducing receptors act to consolidate these states. In this review, the authors experimental results are used to corroborate the hypothesis of divergent modulatory integration. Haloperidol catalepsy and pentylenetetrazole kindling and their interactions with learning processes are considered as a behavioral model of divergent modulatory integration.

The ultralow-intensity electromagnetic fields (EMF, frequency of 4200, modulated by a quasistochastic signal in the range of 20-20,000 Hz, power density of 15 microW/cm2, specific body absorption rate up to 4.5 mJ/kg) potentiated the hypnogenic effect of hexenal. The exposure to the EMF shortened the time of falling asleep induced by this drug and increased sleep duration in rats. The exposure to the EMF also potentiated haloperidol catalepsy: it decreased the drug threshold dose and increased the catalepsy duration. The EMF influence on the haloperidol effects was of a prolonged character: it was manifest in a selected suppression of the emotional excitation in the open-field test within 24 hours after the exposure.

The effects of the ultralow-intensity electromagnetic fields (EMF, frequency of 4200 and 970 MHz, modulated by a quasistochastic signal in the range of 20-20,000 Hz, power density 15 microW/cm2, specific body absorption rate up to 4.5 mJ/kg) on the reactions of the central nervous system (CNS) of rats with different types of behavior were studied. Some neurochemical and behavioral mechanisms of rats' reactions were investigated. It was shown that the EMF produce pronounced changes in the state and activity of monoaminergic brain systems. These changes, on the whole, correspond to the alterations at the integrative level (predominantly, of the inhibitory character).

Behavioral and neurochemical reactions of small laboratory animals (mice and rats of different age) under exposure to ultralow-intensity electromagnetic fields (EMF, frequency of 4200 and 970 MHz, modulated by a quasistochastic signal in the range of 20-20,000 Hz, power density 15 microW/cm2, specific body absorption rate up to 4.5 mJ/kg) were studied. The EMF basically inhibited the locomotor and exploratory activity in the "open-field" test. The species- and age-specific features rather than radiation conditions dominated. However, decrease in the EMF frequency considerably intensified the observed effect. Change in animal behavior was accompanied by shifts in neurochemical processes, i.e., sharp activation of serotoninergic and inhibition of morepinephrinergic system.

Rats were divided in two groups by the reaction of emotional resonance (RER): with emotionally positive reactions (I, with fast RER acquisition, up to 100 s) and with emotionally negative reactions (II, with slow RER acquisition, more than 200 s). After the RER acquisition, the activity of 5-hydroxitryptophan (5-HT) system of the I group of animals was lower than in the II group. The activity of noradrenaline (NA) and dopamine (DA) systems of the I group of animals was higher than in the II group. The between-group differences were enhanced by subcutaneous injection of dalargin. In some brain structures dalargin reversed these relations. These findings point to a complicated interpenetrating character of emotionally positive and emotionally negative states. Emotionally positive states include components of emotionally positive states, and emotionally negative states include components of emotionally positive states. Increase in 5-HT activity and decrease in activity of NA, DA, and opioid (OP) systems induce formation of emotionally negative states. Decrease in 5-HT activity and increase in activity of NA, DA, and OP systems induce formation of the emotionally positive state. It is suggested that 5-HT, NA, and DA systems play the central role in the processes of reinforcement, acquire the evaluative function, and are included in realization of all types of behaviors. OP is a primary modulator system which accompanies the unconditioned pain stimulus and connects it with systems of evaluative function.

Passive avoidance reflex was shown to be differently reproduced in rats. The reproduction was more stable in rats with a higher level of learning. Amnestic effects induced seizures were shown to depend on relationships between the intensity of learning and the intensity of seizures. Unconditioned stimuli acting as a reminder decreased the amnestic effects of seizures. Learning process significantly reduced the seizure severity. A dissociated convulsive state was reproduced with the aid of a pharmacological reminder of anxiety formed in the course of learning. Haloperidol produced anxiety and suppressed amnestic effects of seizures, facilitated conditioning in rats with a low level of learning.

In rat brain cortex, haloperidol initiates the long-term potentiation of K(+)-induced Ca(2+)-dependent noradrenaline (NA) and dopamine (DA) secretion in vitro and in vivo. In both cases, the long-term potentiation is caused by the long-term increase in catecholamine content in the NA and DA terminals, as it has been shown in cortical tangential slices. Acute intraperitoneal haloperidol injection (2.5 mg/kg) evokes catalepsy and increases the content of NA and DA in the brain structures with localization of catecholamine receptors on terminals. This increase appears to be caused, predominantly, by modification of the terminal DA receptors, since only a trend to catecholamine increase is observed in the brain structures with a mixed type of NA and DA receptor localization (on somata and terminals). It is suggested that the long-term and diffuse action of haloperidol after its acute administration consists in the anxiogenic reaction and consolidation of catalepsy without an additional procedure of training and in the absence of unconditioned stimulus.

It was shown that the increased brain seizure readiness persisted within 6 months after termination of corazol kindling. Seizures of the same severity as during kindling (corazol injection in a dose of 20 mg/kg) were reproduced by corazol injection in a dose of 30 mg/kg. In contrast to the control rats, in this situation an autoenhancement of seizures was observed in the kindled animals. Acute corazol seizures induced a decrease in Bmax and Kd of 3H-diazepam binding with benzodiazepine receptors (BDR) in the cerebellum of the 10-months-old control rats white the young animals demonstrated only a decrease in Bmax of binding. In 6 months after kindling termination the BDR activity (Bmax) was reduced by one half. However, we think that the increase in Bmax is not responsible for persistence of the increased seizure readiness. It seems possible that down regulation of receptor activity develops independently of kindling but in response to long-lasting corazol application. Probably, Bmax spontaneously decreases after the termination of the long-term corazol application. The single dose of corazol (30 mg/kg) restores the changes in BDR density to the level when seizure readiness has been just fixed (6 months after kindling termination), independently of the primary receptor density.

The acute korazol (pentylenetetrazol) injection (50 mg/kg) induced seizures which were accompanied by a long-lasting (from 30 minutes to 3 days) decrease in benzodiazepine receptor (BDR) density (Bmax) in rat cerebellum without change in affinity. The density of the BDR was normalized on the 7th day after seizure termination. There were no differences in the initial BDR characteristics between the animals more sensitive to korazol (a dose of 25 mg/kg was sufficient for seizure induction) and less sensitive (30 mg/kg were ineffective). The chronic daily (for 24 days) administration of korazol in a subconvulsive dose led to an increase in seizure readiness (kindling). In 30 min after the last korazol injection the BDR density was decreased to the same extent as after the acute 50 mg/kg korasol administration. The BDR density was normalized on the 7th day after kindling. It was demonstrated that the high-dose-induced and after-kindling seizures were underlain by the same mechanisms. The results suggest that the development of kindling depends on the state of the long-lasting receptors rather than the development of kindling forms the long-lasting reactions. The process of summation is at the basis of kindling development. The long-lasting decrease in activity of BDR receptors induced by a subconvulsive dose of korazol is summed with the following effect of the same dose.

Injection of haloperidol (2.5 mg/kg) immediately after elaboration of the passive avoidance conditioned reflex stabilized retrieval of the conditioned reflex on the 2nd, 7th, and 14th days. Catalepsy induced by haloperidol injection was increased after the completion of passive avoidance conditioning. Conditioned reflex retrieval decreased catalepsy which was retrieved without repeated haloperidol injection. In contrast to the control animals, in the animals after conditioning the most pronounced catalepsy was observed immediately after the conditioned reflex retrieval with the following stabilization at the lower level. The auto enhancement of catalepsy retrieval was more expressed on the 14th day (as compared with the 7th day) both in the control and learned animals, but in the latter it did not depend on the testing time (in contrast to the control animals.

Catalepsy induced by a single intraperitoneal injection of haloperidol (2.5 mg/kg) was consolidated and without additional influences and retained within 2 week (being tested on the 2nd, 7th, and 14th days after injection). Enhancement of catalepsy retrieval was observed during testing of the same animals on the 14th day as compared with the 7th day. Maximal catalepsy expression was reached after 2 hours of testing procedure which points to the existence of the mechanism of autoenhancement of retrieval which is probably underlain by the automodulation of the long-lasting modulatory DA receptors. The retrieval of catalepsy is suggested to be induced by a situational conditioned stimulus, since on the 2nd, 7th and 14th days it may be reproduced without repeated haloperidol injection only in the testing box.

The dependence of electrical conduction on current frequency has been studied in thin layers of pure metals at temperatures between 4.2°K and 297°K. The experimental data are given for frequencies up to 2 × 10 6 Hz. The thin layers were made by deposition from vapour on to cover glass substrates in a vacuum of 10 −6 mm of Hg. As shown by the experimental data, the decrease in electrical resistance with the increase of the frequency is more pronounced in layers having large dc resistance. In layers with negative temperature coefficients of resistance, this decrease is more rapid at low temperatures. The relation between the relative change in electrical conductance and the frequency drawn on a double logarithmic scale is a straight line with a slope equal to 2. On the assumption of a granular structure of the layers, an interpretation is suggested for these properties using an equivalent electric circuit consisting of an intergranular resistance, a bulk resistance of the metallic grains, and an intergranular capacitance which depends on the gaps between the grains. In some very thin layers the ac resistance diminishes continuously with the increasing frequency tending towards the value zero. The origin of this anomalous effect can be ascribed to stray capacitances. The estimation of the ratio between bulk and intergranular resistances discussed from the viewpoint of this theoretical circuit is compared with data from magnetoresistance measurements on ferromagnetic layers.

A hypothesis of the role of autoadrenoreceptors in the processes of synaptic depression, facilitation, PSP amplitude stabilization and amplitude increase with the stimulation frequency growth is described by means of a mathematical model. Synaptic depression is realized by activation of alpha-autoadrenoreceptors, synaptic facilitation--by beta-autoadrenoreceptors activation. A "stable secretion zone" is formed between the autoadrenoreceptor activation curves at which noradrenaline secretion is stabilized. Experimental studies of H3-NA secretion from rats cerebral cortex slices showed that autoadrenoreceptors really form a stable secretion zone. The presence of stable secretion zone provides for self-facilitation and stabilization of H3-NA secretion elicited by 5-fold consecutive K+-depolarizations of slices with time interval 30 min. The absence of the stable secretion zone leads to destabilization of H3-NA secretion. With an increase of the stimulation intensity the curves of autoadrenoreceptors activity and stable secretion zone shift toward high noradrenaline concentrations.

The process of noradrenaline secretion regulation by autoreceptors is described in the terms of the stationary-kinetic reaction. Constants of this reaction are determined using the authors' own data. Analysis of the model has permitted explaining some data from literature which were used to refute the principle of noradrenaline secretion self-regulation by autoreceptors.

A procedure has been suggested for simultaneous recording of 14C-noradrenaline active uptake and induced secretion by rat brain synaptosomes. Active noradrenaline uptake was shown to depend on the presence in the incubation medium of Ca2+. Removal of Ca2+ from the incubation medium considerably reduces the intensity of noradrenaline uptake by the synaptosomes. Unlike the induced secretion in potassium depolarization of synaptosomal membranes, spontaneous release of noradrenaline does not depend on the presence of Ca2+ in the incubation medium.

A mathematical model is presented which quantitatively describes the value of secreted mediator and its dependence on the activity of autoadrenoreceptors in the series of presynaptic impulses. Suggestion that the first impulse in the series is the smallest and comes into the zone of sensitivity of presynaptic beta-adrenoreceptor in the model used facilitates the adrenergic synaptic transmission in the series of presynaptic impulsation experimentally described in synapses of vas deference. Conditions determining the synaptic depression and reduction in adrenergic transmission are analysed.

The influence of learning local protein synthesis was studied in the rat hippocampal synaptosomes. It is found that elaboration of two-way avoidance conditioned reflex causes a decrease in ability of hippocampal synaptosomes to include H3-leucin into proteins in experiments in vitro. It is suggested that cyclic adenosin 3'5'-monophosphate plays a definite role in controlling protein synthesis in the nerve endings during different influences including learning because its addition to the incubation medium activates sharply this process.