[Analysis of functional and biochemical changes in feline cerebral hemispheres after subchronic haloperidol administration]. / Analiz funktsional'nykh i biokhimicheskikh izmenenii v polushariiakh mozga u koshek posle subkhronicheskogo vvedeniia galoperiodol.

Feline experiments have revealed that subchronic haloperidol causes asymmetric changes in the mesencephalic levels of dopamine and serotonin and impairs intrahemispheric balance between the dopaminergic and serotoninergic systems. At the same time the neuroleptic increases motor asymmetry, which appears in response to apomorphine, and changes the nature of interhemispheric relationships. The findings suggest that these changes may be one of the causes of extrapyramidal disorders associated with long-term use of the neuroleptic.

[The behavioral and neurochemical changes in rats caused by the subchronic administration of haloperidol]. / Povedencheskie i neirokhimicheskie izmeneniia u krys, vyzvannye subkhronicheskim vvedeniem galoperidola.

Rat experiments showed that subchronic haloperidol enhanced or perverted motor asymmetry appearing in response to apomorphine, resulted in imbalance between the dopaminergic and serotoninergic systems and increased norepinephrine levels. It was concluded that intra- and interhemispheric imbalance might be one of the causes of extrapyramidal disorders associated with the long-term administration of the neuroleptic.

[Behavioral and EEG signs of the convulsive action of kynurenine and quinolinic acid in cats]. / Povedencheskie i EEG-priznaki sudorozhnogo deistviia kinurenina i khinolinovoi kisloty u koshek.

Administration of quinolinic acid but not L-kynurenine into the cat caudate nucleus was found to produce the appearance of epileptiform charges in the EEG with concomitant behavioral convulsions. A combination of quinolinic acid injections with systemic administration of penicillin resulted in the development of the status of myoclonic convulsions alternating with generalized tonicoclonic seizures. These states were eliminated by diazepam. The right caudate nucleus was revealed to be more sensitive as compared to the left one to the convulsant action of combined administration of quinolinic acid with penicillin.

[Pharmacological analysis of the anticonvulsant action of kavinton]. / Farmakologicheskii analiz protivosudorozhnogo deistviia kavintona.

In experiments on rats it was found that cavinton administered in doses of 1-30 mg/kg exerted a distinct dose-dependent anticonvulsant effect, according to the test of maximal electroshock, not less than that of phenobarbital, difenin and carbamazepine. Combined use of cavinton and these drugs potentiated its anticonvulsant action. The involvement of noradrenergic systems, in particular, alpha 1-adrenoceptors, in the anticonvulsant effect of cavinton is suggested.

[Complex approach to evaluating the antipsychotic properties of neuroleptics modeled on fenamine sterotypy in cats]. / Kompleksnyi podkhod v otsenke antipsikhoticheskikh svoistv neiroleptikov na modeli fenaminovoi stereotipii u koshek.

It was shown that the ability of neuroleptics to cause the high-amplitude wave bursts in sensorimotor cortex in cats with phenamine stereotypy may indicate antipsychotic properties of the drugs whereas suppression of motor automatism largely testifies to their extrapyramidal effects.

[Changes in cat behavior as affected by intracerebral microinjections of kynurenine and quinolinic acid]. / Izmeneniia povedeniia koshek pod vliianiem vnutrimozgovykh mikroin"ektsii kinurenina i kholinovoi kisloty.

Behavioural changes induced by microinjections of neuroactive tryptophan metabolites: L-kynurenine sulfate (KYN, 50-1,000 micrograms) and quinolinic acid (QA, 20-1,000 micrograms) were studied in chronic experiments on cats with cannulas implanted into nuclei caudati. Unlike KYN, whose effects were scarce and nonspecific, QA (500 and 1,000 micrograms) produced marked motor and emotional shifts. The effects were manifested in contralateral rotatory movements, limb hyperkinesis, emotional strain, malice, fear, aggression with snarling and hissing, attack on provocation. It is suggested that kynurenines and QA can participate in the generation of emotional disorders peculiar for epilepsy.

[Effect of Cavinton on convulsions caused by chemical substances]. / Vliianie kavintona na sudorogi, vyzvannye khimicheskimi veshchestvami.

Cavinton was shown to protect mice against convulsions induced by corazol, strychnine and thiosemicarbazide. In addition, cavinton exhibited a definite antagonism to convulsive reactions produced by systemic administration of penicillin to cats and a combined administration of penicillin (intramuscularly) with tryptophan metabolite, quinolinic acid (intracerebroventricularly). The anticonvulsant action of cavinton is suggested to be due to the involvement of the brain GABA- and serotonergic mechanisms. It is reasonable to test cavinton as a drug for treating some forms of epilepsy.

[Dissociation between movement disorders and EEG shifts in amphetamine-induced stereotypy in the cat]. / Dissotsiatsiia mezhdu dvigatel'nymi narusheniiami i sdvigami na EEG pri fenaminovoi stereotipii u koshek.

In experiments on cats it is established that between the degree of EEG desynchronization in the sensorimotor cortex and expressiveness of the stereotype movements, a dissociation is possible which is most distinctly revealed in comparative studies of haloperidol, clozapine and metoclopramide--neuroleptics with different correlation of antipsychotic and extra-pyramidal properties. Local destruction of the ventral parts of the caudate nucleus head enhances motor disturbances resulting from amphetamine administration, but weakens its effect on the cortex. Elimination of the dorsal parts produces an opposite effect. It is suggested that the cause of the dissociation consists in different sensitivity to amphetamine of the dorsal and ventral parts of the neostriatum which are differently involved in organization of stereotype movements and EEG disturbances in amphetamine stereotypy.

[Use of cavinton in epilepsy]. / O primenenii kavintona pri épilepsii.

The authors studied the effect of cavinton (15-45 mg/day) and its combinations with different anticonvulsants on the time-course of different forms of epilepsy. In 20 of the 31 patients studied treatment with cavinton either significantly decreased the frequency of attacks or led to their complete disappearance; in 7 patients the improvement was insignificant and in 4 the condition deteriorated. The greatest effect of cavinton was observed in generalized tonic-clonic convulsions and when they were combined with absences. Clinical improvement not always correlated with EEG normalization. A suggestion is made that the mechanism of the anticonvulsive action of cavinton may be explained both by the normalization of the cerebral blood flow and elimination of hypoxia and by the fact that the drug may possess anticonvulsive properties unrelated to the normalization of the cerebral hemodynamics.

[Characteristics of the effect of haloperidol and clozapine on the rhythmic features of phenamine sterotypy in cats]. / Osobennosti vliianiia galoperidola i klozapina na ritmicheskie kharakteristiki fenaminovoi stereotipii u koshek.

Experiments on cats with the use of an electromechanical rotameter enabling one to separately record head turns to the right and to the left were made to examine the action of the neuroleptics on the time-course of changes in the horizontal component of amphetamine stereotypy. It was shown that haloperidol which destabilizes the oscillatory curve of the rate of head turns led to a progressive decrease in the number of movements. Clazapine also destabilized the rhythmic process. However, increasing the amplitude of oscillations the drug made the curve phasic in nature. Both the neuroleptics caused synchronization of the oscillation rate of head turns to the right and to the left.

[Fenamin stereotypy as a stable rhythmic process]. / Fenaminovaia stereotipiia kak ustoichivyi ritmicheskii protsess.

In cats with amphetamine stereotypy, the rate of horizontal head movements ranges rhythmically in time. Marked stereotypy is in agreement with more regular and low amplitude waves on the total activity curve. During amphetamine effect abatement, the curve gets stabilized as regards the amplitude and period. According to the results of separate evaluation of the temporary dynamics of the number of the left- and right-handed head movements, stereotypy is marked by an increase in the period duration when the rate of the movements changes differently. Natural or neuroleptic-induced abatement of stereotypy is accompanied by an increase in the duration of unidirectional (synchronized) shifts of the rate of the head movements.

[Dynamics of interhemispheric asymmetry in fenamine stereotypy in the cat]. / Dinamika mezhpolusharnoi asimmetrii pri fenaminovoi stereotipii u koshek.

Stereotyped behaviour induced by d,1-amphetamine in cats is a stable rhythmical process. Expressed stereotypy is characterized by stabilization of the summate curve of motor activity fluctuations by amplitude and periods with different asynchronous changes in the number of the left and right head turnings. Low-frequency stimulation of the caudate nucleus and administration of neuroleptics (haloperidol and clozapine) facilitate destabilization of the fluctuations curve and synchronize changes in the frequency of the left and the right head turnings. Structural or functional elimination of the ventrolateral part of the caudate nucleus head leads to opposite effects. It is suggested that amphetamine-induced stereotypy may be due to dynamic dissociation in time of activity of nigro-striatal systems of both cerebral hemispheres.

[Different role of various regions of the caudate nucleus in phenamine-induced stereotyped behavior in cats]. / Neodinakovoe uchastie razlichnykh otdelov khvostatogo iadra v fenaminovoi stereotipii u koshek.

Electrolytic ablation of the ventral parts of the cat caudate nucleus head results in an increase of frequency and disorganization of the pattern of the stereotype head turnings, induced by large doses of amphetamine. Lesion of the dorsal parts, on the other hand, is attended with a decreased number and limited manifestation of stereotype movements. A similar effect appears following a low frequency electrical stimulation of the nucleus ventral part. The disrupting action of neuroleptic haloperidol on the amphetamine-induced stereotype is weakened in animals with ventral lesions and enhanced in those with dorsal lesions. Due to dopaminergic activity, the amphetamine, apparently, produces a functional unbalance between different zones of the caudate nucleus, which underlies stereotype behaviour.

[Effect of phenamine and haloperidol on stereotyped behavior in response to electric stimulation of the substantia nigra in cats]. / Vliianie fenamina i galoperidola na stereotipnoe povedenie, voznikaiushchee u koshek pri élektricheskom razdrazhenii chernoi substantsii.

On being given in low doses (0.25 mg/kg) amphetamine potentiates stereotyped behavior induced in cats by stimulation of substantia nigra. As the dose is raised the effect increases eventuating in the formation of the typical amphetamine-induced stereotypy. Little doses of haloperidol (0.03-0.06 mg/kg) reduce the behavioral and electroencephalographic signs of nigral stereotypy. Amphetamine potentiates, while haloperidol reduces the impairment of the restrained function of the caudate nucleus which occurs in the presence of nigral stereotypy.

[Effect of stimulation and destruction of the substantia nigra on phenamine- and apomorphine-induced stereotypy in cats]. / Vliianie stimuliatsii i razrusheniia chernoi substantsii na fenaminovuiu i apomorfinovuiu sterotipiiu u koshek.

Electrical stimulation of substantia nigra enhances the behavioral and electroencephalographic parameters of the stereotypy induced by threshold doses of amphetamine (0.5 and 1 mg/kg) but does not produce any effect on apomorphine action (2 and 5 mg/kg). Bilateral electrolytic destruction of the brain structure, on the contrary, reduces the action of amphetamine, especially in the early postoperative period. At the same time the intensity of the apomorphine-induced stereotypy rises. It is concluded that the increased activity of substantia nigra is of crucial significance in the genesis of the amphetamine-induced stereotypy. Meanwhile the effect of apomorphine may be realized without direct participation of the brain structure under consideration.

[Possible discrepancy between behavioral adequacy and motor automatisms in cats with phenamine-induced stereotypy]. / Vozmozhnoe nesootvetstvie mezhdu adekvatnost'iu povedeniia i dvigatel'nymi avtomatizmami pri fenaminovoi stereotipii u koshek.

Experiments in cats were made to study the effect of the increasing doses of the neuroleptics haloperidol and clozapin as well as those of metoclopramide with weak antipsychotic properties on various characteristics of amphetamine-induced stereotypy. Haloperidol was shown to return the animals' behavior adequacy to normal and to concurrently eliminate the motor automatisms. Clozapin produced an earlier recovery of the psychoemotional state, exerting a less powerful effect of motor manifestation of stereotypy. On the contrary, metoclopramide eliminated motor disorders more readily but did not return the behavior adequacy to normal. The reason for dissociation of both the characteristics of stereotypy may lie in dissimilar participation in it of different parts of the caudate nucleus or in different implications of the caudate and extracaudate mechanisms.

[Stereotypical behavior developing after electric stimulation of the substantia nigra in cats]. / Stereotipnoe povedenie, voznikaiushchee pri élektricheskom razdrazhenii chernoi substantsii u koshek.

A weak unilateral electrical stimulation of pars compacta of substantia nigra in cats provokes a stereotype behaviour, by its pattern resembling stereotypy induced by amphetamine. During poststimulatory stereotypy, there is a weakening of the arrest reaction induced by low-frequency stimulation of the caudate nucleus. Low doses of haloperidol which do not disturb the spontaneous behaviour, readily weaken trace nigral stereotypy. Such a response may be due to enhancement of nigro-striate dopaminergic transmission and the subsequent limitation of the caudate nucleus restraining function.

[Neurophysiologic and pharmacologic evidence of autoregulationin the nigrostriatal system]. / Neirofiziologicheskie i farmakologicheskie dokazatel'stva samoreguliatsii v nigro-striatnoi sisteme.

Repeated electrical stimulation of substantia nigra in cats produces a progressive relaxation of the poststimulation stereotyped behavior. This effect may be consequent on the development of autoinhibition in the nigro-striatal pathways since the rate of stereotypy inhibition increases in the presence of low doses of amphetamine and apomorphine but is reduced by little doses of haloperidol. A possible reason for autoinhibition is likely to involve an activation of the presynaptic dopaminergic receptors on nigro-striatal axons.

[Influence of GABA-ergic substances on the effects of caudate nucleus stimulation and fenamin stereotyping in cats]. / Vliianie GAMK-ergicheskikh veshchestv na éffekty stimuliatsii khvostatogo iadra i fenaminovuiu stereotipiiu u koshek.

Arrest reaction, circling, cortical spindles induced by electrical stimulation of the caudate nucleus and stereotypy behaviour provoked by threshold doses of amphetamine were recorded in chronic experiments on cats. Sodium hydroxybutyrate and phenibut facilitated motor arrest, while qammalon did not exhibit such an effect. All the substances markedly decreased thresholds of cortical caudate-induced spindles. In contradistinction to gammalon, sodium hydroxybutyrate and phenibut weakened stereotypy behaviour at the same doses of amphetamine that were used in controls, and also interfered with an inhibitory effect of the psychostimulant on the reactions induced by stimulation of the caudate nucleus. It is suggested that the drugs while dopaminergic mechanisms of the neostriatum.