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The first spike-wave discharges (SWDs) in WAG/Rij rats begin to appear at age of 2-3 months and are fully manifested by 5-6 months. Occurrence of SWDs in the EEG is the main indicator of absence epilepsy. Extensive absence epilepsy in 5-6 months-old WAG/Rij rats is accompanied by decreases in dopamine and its metabolites concentrations in the meso-cortico-limbic and nigro-striatal dopaminergic brain systems, resulting in the expression of depression-like behavioral symptoms. In 36 day-old WAG/Rij rats, SWDs are not manifested, deficiency of dopamine is not revealed, and symptoms of depression-like behavior are not expressed. In this study, behavior and monoamines and their metabolites concentrations were investigated in 5 brain structures (prefrontal cortex, nucleus accumbens, hypothalamus, striatum, hippocampus) in 2 month-old WAG/Rij rats in comparison with Wistar rats of the same age. Reduction of the dopamine and its metabolites concentration in 2 month-old WAG/Rij rats was found only in the prefrontal cortex, indicating rapid response of the prefrontal cortex or its high sensitivity. Rapid response of the prefrontal cortex is supposed to be a.fundamental property of this brain structure. Decreases in the dopamine and its metabolites concentration in the prefrontal cortex in 2 month-old WAG/Rij rats were associated with features of behavior which can be regarded as a state of so called pre-pathology (increased anxiety and stress reactivity) preceding the development of depression-like behavior typical for 5-6-months old rats of this strain.

Experimental treatment (long-term fractionated γ-irradiation, antiorthostatic hypodynamia, and the combination of these factors) simulating the effect of space flight in ground-based experiments rapidly restored the motor and orienting-investigative activity of animals (rats) in "open-field" tests. The study of the dynamics of discriminant learning of rats of experimental groups did not show significant differences from the control animals. It was found that the minor effect of these factors on the cognitive performance of animals correlated with slight changes in the concentration ofmonoamines in the brain structures responsible for the cognitive, emotional, and motivational functions.

Effects of 1.5 and 3 Gy from high-energy protons (165 MeV) on rat's motor and oriented trying activities, rate of the Y-labyrinth learning with electric pain stimulation, and levels of monoamines and their metabolites in different brain structures were studied. The experimental results showed that irradiation with these proton doses caused considerable inhibition of the motor and oriented trying activities, and strengthening of passive defense reactions in the open field test; however, no significant change was induced in the learning rate or monoamines turnover. Apparently, emotional and motivational systems were affected to a greater degree than cognitive functions.

The review is devoted to analysis of the basic links of motor behavior control systems: sensorimotor cortex, cerebellum, a red nucleus and striatum. The organization and communications of these structures and their participation in learning and memory processes are described. The synaptic neurotransmitter and nonsynaptic neuromodulatory systems innervating these structures are also described. Hierarchical synaptic networks are formed by GABA and glutamatergic systems. The nonsynaptic dopaminergic system innervates both of these structures, but carries out a modulatory function. The mesocorticolimbic dopaminergic system induces an emotional and motivational state - processes of reinforcement, and participates in realization of purposeful behavior. The nigrostriatal dopaminergic system, through triggering an endocellular signal and the processes ofphosphorylation and dephosphorylation modulates activity ofGABA and glutamatergic receptors ofdorsal striatum spiny neurons and adapted thalamocortical networks.

Chailakhyan's views of sources of the origin of consciousness and mentality have been analyzed. It is supposed that the information interaction alone is not sufficient for the occurrence of consciousness. Something else is necessary that distinguishes a live system from lifeless and can be transmitted to the progeny and evolve. It is assumed that this is an "information-physical interaction", namely, a power profile of conformational reorganizations of proteins during their interaction. L.M. Chailakhyan proves the point of view that this profile during the interaction of proteins cannot be calculated and therefore cannot be cognized. This conclusion is supported by the Godel theorem of incompleteness.

In work the molecular structure and function of GABA(A)-receptor, dependence of allosteric regulation features from subunit composition of receptors are described. Processes of GABAA-receptor plasticity at kindling are described. The process of GABA(A)-receptor allosteric plasticity by pentylenetetrazole (PTZ) kindling induced automodification of receptor activity and consolidated (keeps by means of updating of an expression of genes) its activity. In some days activity of a receptor is restored to a test objective level. In 6 months PTZ subconvulsive dose administration of kindling rats reproduced the severity of seizures and restored of GABA(A)-receptor activity to the level found 6 months before, at the time of termination of kindling, independent of receptor presence activity and age changes. GABA(A)-receptor activity is consolidated by modification of receptor molecule, it is probably by receptor subunit compositions. The study of learning, memory and PTZ amnesia processes have allowed to make a conclusion that similar mechanisms of GABA(A)-receptor plasticity underlie of learning and memory processes. On the basis of the described results the scheme of intraneuronal modulators integration or integration of transduction signals are described.

In this paper a structure of a microdialytic cannula inserted into brain areas just before a microdialysis is described. The cannula used allowed to find out a correspondence of behavioral and biochemical changes in C57BL/6 mice at various time intervals after a single dose administration (20 mg/kg) of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, without any additional pharmacological actions enhancing an extracellular striatal dopamine concentration. Immediately after 1-methyl-4-phenyl-1.2,3.6-tetrahydropyridine administration an essential disturbance of mice behavior and a significant reduction of the extracellular concentration of dopamine and homovanillic acid were observed in striatum. A week after the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration neither behavior nor the extracellular dopamine and homovanillic acid striatal concentration substantially differed from those of controls. 30 days after the neurotoxin administration there was again an essential disturbance of behavior and the large reduction of dopamine and its metabolite concentration in striatum. There was suggested that a reduction of the dopamine concentration immediately after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection connected with abnormalities of dopamine synthesis and metabolism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine whereas a reduction of the extracellular striatal dopamine concentration 30 days after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration related to damage of the nigrastriatal dopaminergic system.

The current review describes the modem Parkinson's disease models in animals, their advantages, limitations and disadvantages. It was noted that the most widespread up-to-date models based on etiology of the Parkinson's disease. Although toxins mostly produce the Parkinson's disease, a study of involved genes allows investigating not only inherited but also sporadic (not inherited) forms of disease since the same genes are involved in both cases. Mutations of genes lead to formation of "mutant" toxic proteins, which produce a death of the specialized neurons of the nigrostriatal dopaminergic system and the development of Parkinson's disease. A significant place in the review takes adescription of characteristics of the toxic models produced by 6-OHDA, MPTP and rotenone, their similarities and differences in pathogenetic mechanisms of the Parkinson's disease development. On the basis of the considered experimental models of Parkinson's disease a conclusion has been done that none of these models may in full and adequate scale imitate the entire clinical, pathophysiological, morphological, biochemical and other aspects of the Parkinson's disease development.

A number of published studies reported a correlation between the paw preference in mice and asymmetry of tissue concentrations of dopamine (DA) and DA metabolites measured in the nucleus accumbens (NAcb) the DA concentration being higher in the nucleus ipsylateral to a preferred paw. This study aimed to investigate whether such asymmetry existed in rats. The paw preference was defined by reaching into a small horizontal tube for a food pellet. Tissue concentration of DA was measured by high-performance liquid chromatography with electrochemical detection. It was shown that the DA concentration in the left NAcb was significantly higher in "left-handed" rats than in "right-handed" animals. Within the group of "right-handers", the DA concentration was significantly higher in the right NAcb than in the left NAcb. The results confirm in part the experimental data obtained in mice and support the hypothesis that the paw preference is paralleled by elevated tissue DA in the ipsylateral NAcb of rodents.

In this paper we have attempted to relate and explain the activity of the brain different integrative levels, which ends up with occurrence of a goal-directed behaviour and reinforcement. Two main mechanisms of responding to subjects and events of external environment, as rapid executive reactions and slow motivational-emotional states, have been marked out. Each mechanism gets its own neurochemical basis, ways of information transmission and molecular-genetic programs for the specialized metabolic reactions. Together both mechanisms form a unique spatial-temporal continuum of neural processes aimed to produce the beneficial activity and reinforce it by subjectively perceived emotional states.

The chronic (21 days duration) administration of tricyclic antidepressant melipramine of Wistar rats strain (15 mg/kg daily, intraperitoneally) evoked weight loss of animals. The 7 days after melipramine abolition its sedative effect was observed in the "open field" test by decrease of locomotion and the number of boles. The 7 and 14 days after melipramine abolition the difference between control and melipramine treated animals in passive and active avoidance learning and memory not found. The experimental results comparison with the literature data show, that chronic melipramine administration of intact animals evokes a sedative state. This conclusion does not contradict to idea of punishment function of brain serotoninergic system.

The administration of threecyclic antidepressant melipramine to Wistar rats (15 mg/kg, intraperitonaly, 2 h before of experiments) increases time of an "open field" centre leaving. Thus melipramine does not influence horizontal and vertical activity, and also the number of bolus. At the development of a passive avoidance conditioned reflex melipramine significantly slows down realization of a unconditional mink reflex by untrained rats, increasing the latency of call in a dark compartment of the chamber. After training significant deterioration of a reflex reproduction is observed. At research of a defensive conditioned reflex of active avoidance melipramine worsens both development and reproduction of a reflex. The comparative analysis of the literary data of imipramine action on uptake of serotonine and noradrenaline and the analysis of the literary data on a role of these systems in the processes of learning and memory allows to suggest, that the effect of melipramine is connected mainly to amplification activity of serotoninergic system of a brain. It is supposed, that acute administration of melipramine creates emotionally negative state, worsens processes of learning and memory, strengthening mainly activity of a brain serotoninergic system. It specifies that serotoninergic system of a brain is system of punishment. Its activation interferes with formation and consolidation of connections between conditional and unconditional irritation.

Comparative analysis of behaviors of two rat strains, Wistar and WAG/Rij, was performed. No behavioral differences between Wistar and WAG/Rij were found in the emotional resonance test. Disulfiram injection produced similar effects in both rat strains. Animals of the first group (with slow acquisition of emotional resonance reaction) transformed into the animals of the second group (with fast acquisition). Passive avoidance conditioning was successfully reproduced in Wistar and was significantly impaired in WAG/Rij. A low dose of disulfiram injected before or immediately after conditioning substantially improved the reproduction to a greater extent in WAG/Rij than Wistar strains thus eliminating in interstrain differences. Active avoidance conditioning was more successful in WAG/Rij than in Wistar rats However, on the next day conditioning in WAG/Rij was substantially impaired. Administration of the low dose of disulfiram or L-DOPA prior to conditioning impaired the acquisition but improved the reproduction on the following day in both strains, but disulfiram injection after conditioning improved conditioning in WAG/Rij to a greater extent than in Wistar. Thus, the pharmacologic enhancement of the reward system substantially changed animal behavior and improved memory consolidation.

Wistar rats were injected with haloperidol (3.5 mg/kg) that resulted in a high level of cataplexy. Next day after haloperidol injection rat behavior was studied in the open field. The animals were divided in two groups. The first group of animals was tested in the daylight without additional illumination of the open-field chamber. The second group was tested in a darkened room with additional intense illumination of the open-field center with a 60W bulb. The testing time was 240 s. The high level of the open-field locomotor activity in the first group was attributed to anxiety. The low level of locomotor activity in the second group was qualified as depressive state.

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.

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.

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.

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.