[Changes in neuroglial interactions in the cerebral nigrostriatal structures in a model of dopamine system dysfunction].

Hypofunction of the dopamine system was induced by haloperidol or reserpine in Wistar rats. Reserpine increased a number of glial fibrillary acidic protein (GFAP) containing astrocytes by 49% and reduced glutamine synthase astrocytes and monoamine oxidase activity by 23% and 1/3, respectively. Haloperidol had no effect on morpho-chemical characteristics of astrocytes but increased a number of oligodendrocytes. It has been supposed that the activation of astroglia by reserpine in a dopamine hypofunction model is caused by the dysfunction of the corticostriatal glutamatergic system as a result of inhibition of the dopaminergic transmission in the basal nuclei. The changes in the neuroglial interactions in the striatum that lead to the disbalance of neuromediator systems in the basal nuclei may underlie the dysfunction of the basal nuclei in some diseases including Parkinson's disease.

[The positive effect of short-term haloperidol administration on the dysfunction of brain metabolism and neuronal activity].

Chronic amphetamine injection increased spontaneous neuronal activity in sensomotor cortex and decreased spike activity in caudate nucleus. The neuronal ability to perform the conditioned reactions was greater in the cortex and smaller in the nucleus caudatus. By biochemical investigations it was showed the hyperactivity of dopaminergic system in the caudate nucleus compared to that in sensomotor cortex. During chronic amphetamine administration haloperidol caused effects similar to the ones caused by amphetamine on neuronal spike activity in sensomotor cortex and did not influence spike activity and neuronal conditioned reactions in the caudate nucleus. The short-term haloperidol action reduced the enzymes activity and particularly the biogenic amines level leading to the normalization of transmitter metabolism.

Effects of short-term exposure to haloperidol and reserpine on dopamine turnover in nigrostriatal system in rat brain.

Spectrophotometric methods were employed to determine activity of dopamine metabolism enzymes, tyrosine hydroxylase and monoamine oxidase B, in nigrostriatal structures of the brain in Wistar rats after short-term (60 min) haloperidol or reserpine treatment. Activating effect of the test compounds on dopamine synthesis, more pronounced in the caudate nucleus, was demonstrated. Utilization of monoamine oxidase B transmitter was activated by haloperidol, but not reserpine. Some peculiarities of response of the nigrostriatal system structures to the test compounds were noted. We hypothesized the presence of a phase of dopamine metabolism activation, aimed at maintenance of dopamine transmission and nervous system adaptation at early terms after reserpine and haloperidol administration.

Structural, functional, and biochemical changes in the brain during modeling of dopamine system disturbances in rats.

Dysfunction of the dopamine system was modeled in Wistar rats by injection of 50 mg/kg L-dopa over 4 weeks. Experimental rats demonstrated considerably decreased locomotor activity and increased emotional strain compared to the control group. Structural changes consisted in a significant decrease in the size of neuronal bodies in the sensorimotor cortex (layers III and V) and caudate nucleus together with changed variability of these parameters compared to the corresponding values in the control. The neuroglial index increased by 22% in layer V, tended to decrease in layer III, and remained unchanged in the caudate nucleus. L-Dopa changed specific activity of enzymes: tyrosine hydroxylase activity in the sensorimotor cortex decreased by 25%, while monoamine oxidase B activity in the caudate nucleus increased by 33%. Thus, dysfunction of the dopamine system resulting in changes in dopamine metabolism not only leads to structural and functional rearrangements reducing functional capacities of the cell systems, but is also associated with compensatory and repair reactions in the brain.

[The influence of amphetamine on changes in the brain neuromediator metabolism].

Vistar rats (stress resistant) and August rats (stress-sensitive) were injected with one-time d,l-amphetamine dosages of 1,0 and 2,5 mg/kg. Specific activity of enzymes involved in dopamine and serotonin metabolism - tyrosine hydroxylase, tryptophan hydroxylase, monoaminooxidase, types A and B - was determined and l-dioxyphenylalanine content measured in brain subfractions (sensomotor cortex and striatum). August rats differed from Vistar rats by enzyme activity indices as well as by neuronchemical index expressing a ratio of the specific activity indices of enzymes studied in the sensomotor cortex and the striatum. The neuronchemical index allowed to reveal the characteristic imbalance of dopamine and serotonin metabolism between the cortex and subcortical regions in the brain of August rats that, apparently, determined their stress sensitivity and clearly demonstrated the peculiarities of different amphetamine dosage effect on the animal brain neuromediator metabolism with different stress resistance.

[The peculiarities of long-term amphetamine action on some brain enzyme systems].

The enzyme activity of serotonin and dopamine synthesis--tryptophan hydroxylase and tyrosine hydroxylase respectively--as well as content of dihydroxyphenylalanine (DOPA) in the brain structures of Wistar and August rat strains were studied in normal conditions and during long-term amphetamine administration (21 day) in dosage of 1.0 mg/kg. Between-strain differences were observed both in normal conditions and during amphetamine using. Inhibition of tyrosine hydroxylase activity, decrease of DOPA and activation of tryptophan hydroxylase activity in the brain structures were found in August rats under amphetamine action. On the contrary, inhibition of tryptophan hydroxylase activity, activation of tyrosine hydroxylase activity and increase of DOPA were revealed in Wistar rats. A relationship between neuronmediator systems metabolism in the brain and peculiarities of behavior and emotional reactivity of the animals during pathological influence was demonstrated.

Effect of delta-sleep-inducing peptide on activity of enzymes of biogenic amine metabolism in the brain of Wistar and August rats.

Activity of enzymes catalyzing synthesis and degradation of serotonin and dopamine in brain structures of Wistar and August rats was measured biochemically under normal conditions and after short-term exposure to delta-sleep-inducing peptide. The effects of the test peptide manifested in activation of the serotoninergic system and inhibition of the dopaminergic system, particularly in the caudate nucleus. These changes were most pronounced in the brain of Wistar rats.

[Morphochemical characteristic of rat brain structures after exposure to delta-sleep inducing peptide following long-term amphetamine administration]. / Morfokhimicheskaia kharakteristika struktur mozga krys posle vozdeistviia del'ta-son indutsiruiushchego peptida na fone khronicheskogo vvedeniia amfetamina.

The aim of this work, that was carried out using Wistar rats, was to characterize the response of neurons of different morphofunctional types to amphetamine administration and to study the possibility of correction of these changes by delta-sleep inducing peptide (DSIP). Single intraperitoneal injection of 60 microg/kg of DSIP following a long term amphetamine administration (2.5 mg/kg for 3 weeks) was shown to result in normalization of brain metabolism, that was disturbed by the drug. The correcting DSIP effect was found in rat brain structures judging by the parameters of the state of proteins in neurons of sensomotor cortex and caudate nucleus and by the activity of enzymes of neurotransmitter metabolism, such as type A and B monoamine oxidases and acetylcholine esterase, that was determined in subfractions of the same brain structures. DSIP modulating effect in phenamine stereotypy supports its role as an adaptogen of intercenter relations in CNS pathology.

[Mechanism of nootropic digam action in hypofunction of brain dopaminergic system]. / Mekhanizm nootropnogo deistviia digama pri gipofunktsii dofaminergicheskoi sistemy mozga.

Using microchemical methods for detection of dopamine (DA), noradrenaline (NA), serotonin (S) and its metabolite--5'-hydroxyindolilacetic acid (5'-HIAA) as well as the activity of neuromediator-utilising enzymes--MAO A and B and enzymes of acetylcholine metabolism--cholinacetyltranspherase (ChAT) and acetylcholinesterase (AChE), we revealed that synthetic GABA-derivative compound diagram (250 mg/kg during 10 days) normalized functioning of dopaminergic and acetylcholinergic systems in sensormotor cortex and caudate nucleus of Wistar rats with haloperidol-induced (0.5 mg/kg during 30 days) bradykinesia. Measured by quantitative interpherometric method, a specific response of functionally different sensomotor cortex (layers III and V) neurons and caudate nucleus by such characteristics as cytoplasm and nuclei sizes, protein content and concentration was found. Control for rat's behavior in open field revealed that diagram restored emotional activity disturbed by haloperidol injections and improved the indices of the animals searching activity.

[Amphetamine action on morphochemical brain organization]. / Deistvie amfetamina na morfokhimicheskuiu organizatsiiu mozga.

The activity of enzymatic systems--monoamine oxidase, types A and B, and acetylcholinesterase involved in neuromediator utilisation and their levels correlation in the cortex and caudate nucleus brain tissue subfractions in control and during long (3 weeks) amphetamine (psychostimulator) injections in dosage 2.5 mg/kg were studied. Wistar and August rats different by behavioral characteristics were used. Differences of enzyme activity on subcellular level both in controls and in rats with dopaminergic dysfunction, caused by amphetamine, were found. Comparing to Wistar rats, in August ones characterized by lower motor activity and elevated stress sensitivity, amphetamine caused a significant MAO A and acetylcholinesterase activity inhibition, the changes being more pronounced in the caudate nucleus. It is suggested that the differences of enzymatic activity, reflecting the state of brain neuromediator metabolism and emerging in pathological conditions, may underlie a mechanism of CNS psasticity.

[The experimental development of the concept of O. S. Adrianov on the correlation of functional and neurochemical processes: regulatory peptides in mediator system dysfunction]. / Eksperimental'noe razvitie kontseptsii O. S. Adrianova o sootnoshenii funktsional'nykh i neirokhimicheskikh protsessov: reguliatornye peptidy pri disfunktsii mediatornykh sistem.

The article is devoted to commemoration of full member of Russian Academy of Medical Sciences, Oleg Andreevich Adrianov, who would have celebrated his 75-th anniversary in 1998. O. S. Adrianov, author of numerous works on physiology and morphology of central nervous system, in the recent years of his was studying the problem of the processes relationship at macro and micro levels of brain organization. Further to the concept created by O.S. Adrianov, data on action of two peptides: delta-sleep and tafcine, on behavior, neurophysiological and neurochemical processes have been consolidated. Experimental data were obtained for rabbits, cats, and dogs, both intact and in the state of pathology (psychomotoric excitement, bradykinesia, penicillin epilepsy). Impact of peptides on convergation processes is discussed: peptide of delta-sleep depresses reactions of brain structures to photo- and phono-stimulation, and activates the serotoninergic system in general; tafcine enforces the convergation processes and activates the dopaminergic system.

Metabolism of neurotransmitters in cortical and subcortical brain structures in rats with different behavioral characteristics.

Experiments were performed on Wistar rats with high and low locomotor activities. In rats with high locomotor activity, activities of acetylcholine transferase, acetylcholine esterase, and monoamine oxidase A increased in the subcellular fractions of the sensorimotor cortex and arcuate nucleus, while monoamine oxidase B activity decreased compared to those in rats with low locomotor activity. The peculiarities of neurotransmitter systems in brain structures of rats with different behavioral patterns were related to genetic and functional organization of the central nervous system.

Regulation by delta-sleep-inducing peptide of the neurochemical changes in the brain associated with dopaminergic system hyperactivity.

The influence of a single injection of "delta-sleep-inducing peptide" (DSIP; 30 microg/kg body weight) on neurochemical parameters of rats' brain was studied under the conditions of chronic administration of dopamine analogs inducing DA-system hyperactivity - 50 mg/kg body weight of L-DOPA for 30 days or 2,5 mg/kg body weight of amphetamine for 21 days. The parameters of serotonergic system (MAO A activity, 5-HT, and 5-HIAA contents) and of dopaminergic system (MAO B activity, DA, NA, and HVA contents) were investigated in the cortex and caudate nucleus of control, DA or amphetamine, and DSIP receiving rats. Changes caused by the two DA-system activating drugs had both similarities and differences, and the corrective action of DSIP also had certain peculiarities depending on the pharmacological preparation used for the induction of DA-system hyperactivity and on the investigated brain structure. It is supposed that DSIP action might be based on the activation of serotonergic system that ensures the adaptive behavior of the animals.

[The neurochemical and behavioral indices of an acquired alcohol craving in rats under conditions of information loading]. / Neirokhimicheskie i povedencheskie pokazateli priobretennogo vlecheniia k alkogoliu u krys v usloviiakh informatsionnykh nagruzok.

The state of neurotransmitter systems was studied in the groups of Wistar rats discriminated by striving for alcohol and rejecting it after the information load (alimentary instrumental conditioning in a labyrinth). The specific activities of neurotransmitter metabolizing enzymes (MAO A and B, acetylcholinesterase, and acetylcholinetransferase) and the content of biogenic amines and their metabolites (serotonin, 5-hydroxyindoleacetic acid, noradrenaline, and dopamine) were measured in homogenates and subfractions of sensorimotor cortex and caudate nucleus. It was found out that the biochemical indices correlated with cognitive abilities of animals. Stress-resistant rats, which were capable for acquisition of the complex skill, refused alcohol after the information load and were characterized by activation of the brain neurotransmitter systems. The rats, which were unable to fulfill the cognitive task, began to abuse alcohol and were characterized by suppression of the neurotransmitter systems. It seems possible that the brain neurotransmitter metabolism adequately reflects the characteristics of the higher nervous activity of animals and their resistance to alcohol.

[The activity of the neuromediator systems in the cortex and caudate nucleus in rats with different degrees of initial alcohol preference]. / Aktivnost' neiromediatornykh sistem v kore i khvostatom iadre mozga krys s raznoi stepen'iu iskhodnogo predpochteniia alkogolia.

The study was made of functional state of catecholamine, dopaminergic, serotonergic and cholinergic cerebral systems in terms of the activity of some enzymes of neuromediator metabolism, the content of biogenic amines and their correlation in brain and cerebral caudate nucleus. 3 groups of rats with different initial craving for alcohol were examined: rejecting alcohol (RA); consuming it but without preference (WAP); and rats preferring alcohol under the conditions of free choice between water and alcohol (PA). Peculiarities of the functional state of the systems studied depended on the degree of the preference to alcohol. The main changes in PA rats, as compared with RA group, manifested as a decrease of corresponding indices. That confirmed a different degree of the inhibition of their activity as well as alterations in the interaction between neuromediator systems. These changes were more pronounced in the cortex than in caudate nucleus. Such alterations may be related to structural-functional flexibility of CNS and might be the basic mechanism of the genetic predisposition to alcohol consumption.

[Amphetamine-induced hyperfunction of the dopaminergic system and delta sleep-inducing peptide]. / Amfetaminovaia giperfunktsiia dofaminergicheskoi sistemy i peptid del'ta-sna.

Following amphetamine administration, the DSIP aggravated behavioural patterns but the EEG remained unaltered in the visual and motor cortex, and in the caudate nucleus. The findings suggest that the peptides modulating action depends on the way of dopamine hyperfunction initiation.

[The correction of amphetamine action by the delta sleep-inducing peptide]. / Korrektsiia deistviia amfetamina peptidom, indutsiruiushchim del'ta-son.

Effects of "delta-sleep inducing peptide" administration (60 micrograms/kg) to rats on the background of amphetamine action (2.5 mg/kg during 3 weeks) were studied. Activities of the enzymes of neurotransmitter turnover as well as the contents of biogenic amines in structures of motor cortex and caudate nucleus were investigated. Normalizing action of the peptide on the studied indices was found. It reflected the correction of the increased activity of dopaminergic and serotoninergic systems elevated as a result of amphetamine action. The suggestion was made that reconstruction of the interactions of neurotransmitter systems in brain providing adaptive behavior in animals was the main mechanism of delta-sleep inducing peptide's action.