[Rats of Krushinsky-Molodkina strain: studies of audiogenic epilepsy, vascular pathology, and behavior].

Physiological, biochemical and genetic studies of audiogenic epilepsy in Krushinsky-Molodkina (KM) rat strain are analyzed. In brief, the history of KM strain selection and its current state are reviewed. Physiological mechanisms of the typical audiogenic seizure development and the audiogenic myoclonus (audiogenic kindling phenomena) are considered. The EEG correlates of these phenomena are presented. Biochemical features of the strain (neurotransmitter and neuronal membrane biochemistry) are described.

[Remote effects of early postnatal pituitary hormone melatonin injection on audiogenic seizures in Krushinsky-Molodkina rats].

Rats Krushinsky-Molodkina inbred strain (KM) genetically prone to audiogenic seizures were injected with pineal hormone melatonin (50 mg/kg, s.c.) within the period 7th to the 14th posnatal days (PND). The remote effects of this injection adult KM rats consisted in a decrease in the latency and increase in severity of myoclonic seizures produced by audiogenic kindling (20 sound stimuli, 100 dB and 12-15 kHz). As compared to the control, in the cortex and hippocampus of rats of melatonin group, we also found a significant reduction of both total and functional activity of Ca2+/calmodulin-dependent protein kinase II (CAMK II) after audiogenic kindling. On the contrary, melatonin administration within the 1st to 7th PND and the 14th to the 21st PND resulted in a decrease in seizure activity. In the first case, both the total (cortical) and functional (hippocampal) CAMK II activities in melatonin-injected rats were increased as compared to control, whereas in the second case, only a slight increase in Ca2+-independent CAMK II activity in the hippocampus of melatonin-injected rats was observed. Probably, the melatonin administration in the period of early postnatal development changes the features of expression and/or regulation of CAMK II activity, and this could be one of the mechanisms of audiogenic seizure modulation in KM rats.

[Developmental changes in audiogenic epilepsy and myoclonus in KM rats]. / Audiogennaia épilepsiia i mioklonus v ontogeneze krys linii KM.

The reaction to a single sound stimulation (a bell) applied daily and the time of the first appearance of myoclonus were recorded in Krushinsky-Molodkina (KM) rats of different ages (30, 60, and 150-200 days). The audiogenic seizures in adult animals were of short latency and always resulted in tonic convulsions, which were stable in their patten. In contrast, in young animals (in particular, in 30-day-old rats), the seizures were less pronounced and unstable. The daily sound stimulation produced a gradual development of myoclonic seizures in young and adult rats. In old rats, the stable myoclonus appeared on the 17th day of stimulation, and in 30-day-old animals the myoclonus was recorded on the 26th day. In 60-day-old rats the myoclonus appeared for the first time on the 20th day of stimulation. It is suggested that these age differences can be explained by the btain immaturity (in particular, of neurotransmitter system) in young animals.

[The effect of carbamazepine on the content of monoamines and their metabolites in the brain structures of rats with audiogenic epilepsy]. / Vliianie karbamazepina na soderzhanie monoaminov i ikh metabolitov v strukturakh mozga krys s audiogennoi épilepsiei.

It was shown that the content of serotonin (5-OT) and 5-oxyindoleacetic acid (5-OIAA) in the temporal cortex, hippocampus and medulla oblongata and the content of dopamine and 3,4-dihydroxyphenilacetic acid in the striatum are increased initially, while the level of norepinephrine in the striatum is reduced in Krushinskii-Molodkina rats genetically predisposed to audiogenic epilepsy in comparison with Wistar rats. Carbamazepine levelled out the changes in the 5-OT and 5-OIAA levels at the peak of the audiogenic attack in the temporal cortex and hippocampus, causing at the same time a sum increase in the content of all monoamines and their metabolites in the medulla oblongata and striatum.

[The effect of difenin, valproate and phenobarbital on the development of an epileptiform seizure attack in Krushinskii-Molodkina rats]. / Vliianie difenina, val'proata i pentobarbitala na razvitie épileptiformnogo sudorozhnaogo pripadka u krys linii Krushinskogo--Molodkinoi.

The anticonvulsant action of diphenin, sodium valproate, and pentobarbital was studied in Krushinskii-Molodkina (KM) rats subjected to audiogenic seizures. The anticonvulsant effects of the drugs were different and dose-dependent. Valproate in a dose of 120 mg/kg completely eliminated the tonic phase of seizures. Given in a dose of 300 mg/kg it in 50% of cases prevented from the development of the initial seizure stage of motor excitation. The peculiarity of the pentobarbital action consisted in its ability to change the character of motor excitation during sound stimulation from the one-wave reaction for the two-wave.

[The effect of lamotrigine and carbamazepine on the development of the audiogenic seizure reaction in rats of the Krushinskii-Molodkina strain]. / Vliianie lamotridzhina i karbamazepina na razvitie audiogennoi sudorozhnoi reaktsii u krys linii Krushinskogo--Molodkinoi.

The effect of Lamotrigine and carbamazepine on the development and character of the epileptiform seizures after strong sonic stimulation were studied on Krushinskii-Molodkina line of rats. Both drugs manifested a dose-dependent increase in the latency of motor reaction Lamotrigine administration in the dose range of 5-40 mg/kg, i.p., resulted in a moderate decrease in the seizure intensity preventing predominantly the tonic component of the seizure and failed to modify the character of convulsive reaction. Carbamazepine administered in doses of 7.5-30 mg/kg effectively prevented the epileptiform seizures. The "two-wave" motor reaction was observed in 15% of carbamazepine-treated rats.

[A model of audiogenic epilepsy--rats of the Krushinskii-Molodkina strain. Proof of genetic homogeneity]. / Model' audiogennoi épilepsii--krysy linii Krushinskogo--Molodkinoi. Dokazatel'stvo geneticheskoi odnorodnosti.

Genetical homogeneity of Krushinskii-Molodkina (KM) stock was studied by the method of reciprocal transplantation of skin. The rats were selected inside genealogic card from 5 different substrains of the 20th generation of brother-sister crossing (F 20). The tail-to-tail transplantation was made by the scheme of double reciprocal ring in 9 females from the KM stock. Observations within 314 days showed a good condition of the transplants. The obtained data suggest that Krushinskii-Molodkina rats are an inbred strain.

Increase of brain endogenous monoamine oxidase inhibitory activity (tribulin) in experimental audiogenic seizures in rats: evidence for a monoamine oxidase A inhibiting component of tribulin.

Brain tribulin activity in rats with an inherited predisposition to audiogenic epilepsy was studied after seizures of different intensity were induced by an electric bell. Weak seizures (from 0 to 2 arbitrary units) did not produce any changes in endogenous inhibitory activity towards either monoamine oxidase (MAO) A or B. Moderate seizures were characterized by increases in both MAO A and MAO B inhibitory activity (up to 1.9-fold). Complete tonic epileptiform seizures with total areflexia (4 arbitrary units) induced further augmentation (up to 2.5-fold) of MAO A but not of MAO B inhibitory activity. This dissociation between the two inhibitory activities points to the existence of a separate MAO A-inhibiting component of brain tribulin which is different from isatin.

The role of lipid peroxidation in the possible involvement of membrane-bound monoamine oxidases in gamma-aminobutyric acid and glucosamine deamination in rat brain. Focus on chemical pathogenesis of experimental audiogenic epilepsy.

Incubation of rat brain synaptosomes and mitochondria with LPO inducers (Fe2+ and ascorbate) was accompanied by a decrease of deamination of serotonin (substrate of MAO-A) in mitochondria, but not in synaptosomes, with simultaneous stimulation of GABA and GLCA deamination, apparently owing to modification of catalytic properties of brain membrane-bound MAO. Oxidation of PEA (substrate of MAO-B) was insignificantly altered in both fractions. Reactions of deamination of serotonin, GABA, and GLCA (but not PEA), were highly sensitive to a selective inhibitor of MAO-A pyrazidol (pyrlindole). Isoniazid and hydrazides of quinoline carbonic acids (inhibitors of both modified MAO and copper-containing amine oxidases) strongly inhibited deamination of GABA and GLCA. During epileptiformic seizures in rats, genetically selected for high incidence of audiogenic epilepsia, stimulation in brain synaptosomes and mitochondria of LPO was observed. This was accompanied by a marked decrease in serotonin and PEA deamination, with a simultaneous increase in GABA and GLCA deamination in both fractions. The data obtained suggest that appearance of GABA-deaminating activity owing to modification of catalytic properties of MAO, might be an essential pathogenetic component in the development of epileptic seizures.

[Change in the catalytic properties of mitochondrial monoamine oxidase in experimental audiogenic epilepsy]. / Izmenenie kataliticheskikh svoistv mitokhondrial'nykh monooksidaz pri audiogennoi épilepsii v éksperimente.

Catalytic properties of mitochondrial monoamine oxidases (MAO) were studied in brain, heart, liver and kidney of rats of Krushinskii-Molodkina strain with inherited audiogenic epilepsia. In brain of these rats a. 2.5-fold decrease of Vmax of serotonin (MAO-A substrate) deamination has been found. During audiogenic epileptiformic attack 2.5-5-fold decrease of Vmax of serotonin deamination in brain and liver and also decrease of benzylamine (MAO-B substrate) oxidation in brain were found. Simultaneously oxidation of glucosamine and gamma-aminobutyric acid was markedly increased (up to 5-fold and more) in brain. The data obtained showed that qualitative transformation occurred in catalytic properties of MAO which may be an important pathogenic factor in the development of epileptiformic attack.

[The possibilities of correcting some complex behavioral reactions in KM rats by using an antioxidant]. / Vozmozhnosti korrektsii nekotorykh slozhnykh povedencheskikh reaktsii krys KM s pomoshch'iu antioksidanta.

On rats of KM (Krushinskii-Molodkina) line the influence was studied of antioxidant (phenozan-K) on the ability to solve extrapolation task and behaviour in the open field test. It is shown that intraperitoneal injection of the antioxidant in a dose of 30 mg/kg significantly increases the number of individuals solving the extrapolation task at its first presentations and also activates the orienting-investigatory behaviour in the open field test. Proceeding from the supposition about the necessity of sufficiently high (optimum) level of excitability of the central nervous system for realization of mental act, a conclusion is made about the possibility of its correction by means of antioxidants.

[Nonspecific grooming in rats during the solution of an extrapolation task]. / Nespetsificheskii grumming u krys pri reshenii ékstrapoliatsionnoi zadachi.

Grooming behavior in laboratory brown rats was analysed in the course of extrapolation task solving. Cases of task solution (correct and incorrect) were compared with those when animal "refused" to turn round the screen during search of food bait. In latter cases grooming episodes were more numerous, their latency and duration being higher than during former cases. At the same time the latest stages of experiment (when 8-13 trials a day twice a week were presented) were characterized by more frequent grooming occurrence as well as by longer latencies and duration of grooming episodes. When rats were given I trial a day with one week intervals grooming incidence as well as "refusals" occurrence decreased. The possible participation of animal grooming in arranging the defense reactions against excessive and inadequate activity is discussed.

[DNA fingerprinting of Rattus norvegicus: a new approach in genetic analysis]. / Genomnaia daktiloskopiia krys Rattus norvegicus: novyi podkhod k geneticheskomu markirovaniiu.

Recent finding in highly effective DNA probes for RFLP testing (of hypervariable minisatellite DNA type) has led to the invention of DNA fingerprinting--the new technique of great value for identification of individuals, establishing biological kinship and studies in population genetics. We anticipate that DNA fingerprinting procedure with M13 phage DNA as a probe which we have developed earlier, makes it possible to apply new approach in genetic analysis--establishing, whether or not a particular locus is associated with the inheritance of genetic disease, by comparing the whole restriction fragment data from affected and unaffected animals. In this work, using the method described we characterized the Kroushynsky-Molodkina rat strain with hereditary disposition for epileptic attacks and performed comparative fingerprint analysis of these defective and normal rat genomes. The data obtained may hold some promises for further seeking the particular defective gene.

[Participation of the dorsal cortex of the forebrain in the solving by turtles of an extrapolation task during its first and multiple presentations]. / Uchastie dorzal'noi kory perednego mozga v reshenii cherepakhami ékstrapoliatsionnoi zadachi pri pervykh i mnogokratnykh ee pred''iavleniiakh.

In experiments with ablation of the forebrain dorsal cortex in turtles it has been established that this structure plays a significant role in first solving of an extrapolation task (6-19 times) and looses its integrating role at multiple test solving (40-195 times). The obtained data testify to the presence of two types of animals adaptive behaviour in solving the extrapolation task: based on operation with empirical laws of movement and manifested at first task presentations (elementary rational animals activity), and that based on learning and appearing after multiple reiterations of the experimental situation in the form of motor conditioned reflex of passing the obstacle from the corresponding side.

[Features of the dynamics of the forebrain EEG of Emys orbicularis during the solving of an extrapolation problem]. / Osobennosti dinamiki EEG perednego mozga bolotnykh cherepakh pri reshenii ékstrapoliatsionnoi zadachi.

Sharp EEG changes are recorded in bioelectrical activity of the dorsal cortex and dorsal ventricular edge in marsh tortoises in conditions of free movement during solving of an extrapolation task (a test of elementary reasoning ability). These changes of a pathological character, accompanied by neurotic states, were observed in some animals having correctly solved the task several times in succession (2-5), beginning with the first presentation. Such changes of EEG and behaviour were not found in tortoises that committed errors at first presentations of the task and only gradually learned correct solving. Formation of the adequate behaviour can proceed by two means: on the basis of elementary reasoning ability and learning. Disturbance of adequate behaviour in the experiment with characteristic changes of EEG testifies to a difficult state of the animal during solving of the extrapolation task.