Differences in Monoamine Oxidase Activity in the Brain of Wistar and August Rats with High and Low Locomotor Activity: A Cytochemical Study.

Monoamine oxidase activity was quantitatively assessed by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampal CA3 field) of rats of August line and Wistar population with high and low locomotor activity in the open fi eld test. Monoamine oxidase activity (substrate tryptamine) predominated in the nucleus accumbens of Wistar rats with high motor activity in comparison with rats with low locomotor activity. In August rats, enzyme activity (substrates tryptamine and serotonin) predominated in the hippocampus of animals with high motor activity. Comparison of August rats with low locomotor activity and Wistar rats with high motor activity (i.e. animals demonstrating maximum differences in motor function) revealed significantly higher activity of the enzyme (substrates tryptamine and serotonin) in the hippocampus of Wistar rats. The study demonstrates clear-cut morphochemical specificity of monoaminergic metabolism based on the differences in the cytochemical parameter "monoamine oxidase activity", in the studied brain structures, responsible for the formation and realization of goal-directed behavior in Wistar and August rats.

Brain acetylcholinesterase activity in Wistar and August rats with low and high motor activity (a cytochemical study).

Acetylcholinesterase activity was quantitatively evaluated by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampus CA3 field) of August and Wistar rats demonstrating high and low motor activity in the open field test. In August rats, acetylcholinesterase activity in the analyzed brain structures prevailed in animals with high motor activity in comparison with rats with low motor activity. In Wistar rats, the differences between the animals demonstrating high and low motor activity were less pronounced, but varied depending on the experimental series of studies. Comparisons of August rats with low motor activity and Wistar rats with high motor activity (maximum difference of motor function in these animals) revealed significant excess of acetylcholinesterase activity in layer III of the sensorimotor cortex in August rats and no differences in other brain structures of the examined animals.

[Morphochemical characteristics of hippocampal neuron's response to the hypofunction of the dopaminergic system].

Differences in the response of August rats' hippocampal field СА1 and СА3 neurons to the chronic haloperidol administration (a model of parkinsonism) were revealed by interferometric methods. Based on the morphochemical parameters (nuclear and cytoplasmic area, protein content and concentration), the changes of field СА1 neurons can be regarded as functionally active (all parameters are significantly higher than in controls), and those of field СА3 neurons - as initial stages of degeneration (the significant decrease of neuron sizes). The differences in the response found in this study can be associated with the functional characteristics of СА1 and СА3 fields.

Cytochemically determined activity of glucose-6-phosphate dehydrogenase in morphochemical characteristics of the brain of wistar rats differing by locomotion parameters.

Activity of histochemically determined glucose-6-phosphate dehydrogenase, a key enzyme of the pentose phosphate pathway, was qualitatively determined in layer III and V neurons of the sensorimotor cortex and neurons of the caudate nucleus, nucleus accumbens, and hippocampus (CA3) in mature male Wistar rats with high and low locomotor activity in an open field. A negative correlation was revealed between locomotion of Wistar rats in the open field and activity of glucose-6-phosphate dehydrogenase in the sensorimotor cortex, especially in efferent layer V neurons and neurons of the caudate nucleus and nucleus accumbens, which attested to different capacity of the brain in Wistar rats with high and low open-field locomotion to regeneration of phosphopyridine nucleotides (NADP(+)) and production of pentoses via the pentose phosphate shunt.

Morphochemical study of hippocampus of august rats after systemic treatment with amphetamine followed by injection of delta sleep-inducing peptide.

Quantitative interferometry showed that chronic amphetamine administration to August rats (2.5 mg/kg/day for 3 weeks) increased the area of neuronal cytoplasm and nuclei and content and concentrations of proteins in hippocampal CA3 neurons. These changes persisted after single injection of delta sleep-inducing peptide (60 microg/kg). The reaction of the entire neuronal population of hippocampal CA3 neurons to amphetamine is similar.

[Morphochemical analysis of hippocampus of rats predisposed (August) or resistant (Wistar) to emotional stress]. / Morfokhimicheskie razlichiia gippokampa krys, predraspolozhennykh (Avgust) i ustoichivykh (Vistar) k émotsional'nomu stressu.

The aim of this work was the comparative cytochemical study of some parameters of neurotransmitter and protein metabolism in the hippocampus (CA3 field) of August and Wistar rats, which were used as genetic-functional models demonstrating different brain organization, in particular, in respect to an emotional stress. Using quantitative cytochemical methods it was demonstrated that the activities of aminopeptidase, monoaminooxidase (substrates--tryptamine and serotonin), and glutamate dehydrogenase, were lower in the hippocampus of August rats (predisposed to emotional stress) as compared to that one in Wistar rats (resistant to emotional stress). August rats were also characterized by smaller sizes of neuronal cytoplasm and nuclei and by their lower protein content and concentration. The analysis of the data obtained has shown the existence of neurons with different modalities within the limits of CA3 hippocampal field, and these characteristics are thought to define the morphochemical differences in the hippocampus (CA3 field) of genetically different rats.

[Influence of L-DOPA on rat brain depending on individual behavioral features]. / Vliianie L-DOFA na mozg v zavisimosti ot individual'nykh osobennostei povedeniia.

To cause brain dopaminergic hyperactivity in rats, L-DOPA was injected in August and Wistar rats with different basic stress reactivity and motor activity in open field ecperiments during 14 days. L-DOPA was used in the form of the drug madopar in dosage of 25,5 mg/kg of body mass daily. The indices of activity of metabolism enzymes, neuromediators and proteins: aminopeptidase, glutamatedehydrogenase, monoaminoxidase (substrate triptamine) and acetylcholinesterase were studied in sensomotor cortex, caudate nucleus, nucleus accumbens and hippocampus region. The intra- and between-line features of L-DOPA influence on rat brain have been found, being mostly pronounced in the animals with low motor activity. In these rats, changes were observed in all structures and for all enzymes, but in the group with high activity they concerned only GDH in caudate nucleus and nucleus accumbens. Hippocampus was the structure reacting to L-DOPA most actively as shoun by cytochemical indices, with reactions relating mainly to serotonergic system in August rats and to acetylcholinergic and glutamatergic systems in Wistar rats. The results demonstrate an essential role of genetically determined reactivity and motor activity in individual prognosis of resistance to stress and extreme situations.

Neurochemical characteristics of the effects of delta sleep-inducing peptide in Wistar rats with hyperactivity of the dopaminergic system.

Quantitative cytochemical assay showed that single injection of delta sleep-inducing peptide increased monoamine oxidase activity (substrates: serotonin and tryptamine) in the caudate and accumbens nuclei and glutamate dehydrogenase activity in the hippocampus of stress-resistant Wistar rats chronically treated with L-DOPA. Enzyme activities in the sensorimotor cortex did not change. Delta sleep-inducing peptide had no effects on acetylcholine esterase and aminopeptidase activities in the brain of Wistar rats.

[Changes in the enzyme activity in the brain structures of August rats under the influence of the delta sleep-inducing peptide against a background of prolonged L-dihydroxyphenylalanine administration]. / Izmeneniia aktivnosti fermentov v strukturakh mozga krys Avgust pod vliianiem peptida del'ta-sna na fone dlitel'nogo vvedeniia L-dioksifenilalanina.

Quantitative cytochemical methods revealed the decrease of MAO activity (substrate--tryptamine) in the hippocampus of L-dioxytryptamine treated August rats genetically predisposed to emotional stress under the effect of delta sleep inducing peptide (DSIP). Activities of aminopeptidase and glutamate dehydrogenase were decreased in n.accumbens while changes of the activities of these enzymes were not significant in the layers III and V of sensomotor cortex and n.caudatus. In all brain structures Ache and MAO (substrate 5-hydroxytryptamine) activities were not influenced by DSIP.

[Comparative cytochemical study of the central nervous system in Wistar and August rats in dopamine system hyperfunction]. / Sravnitel'noe tsitokhimicheskoe issledovanie tsentral'noi nervnoi sistemy krys Vistar i Avgust pri giperfunktsii dofaminovoi sistemy.

Peculiarities of the CNS response to chronic treatment with L-DOPA were revealed by quantitative cytochemical methods in August (stress-sensitive) and Wistar (emotionally resistant) rats. In August rats L-DOPA administration caused aminopeptidase activity increase in sensomotor cortex layer 3 and nucleus accumbens, glutamate dehydrogenase activity growth in nucleus accumbens as well as the elevation of monoaminoxidase (MAO) activity in nucleus caudatus and nucleus accumbens (serotonin as substrate) and in nucleus caudatus and hippocampus (tryptamine as substrate), while acetyl cholinesterase activity did not change at all. At the same time in Wistar rats only glutamate dehydrogenase activity increase was observed in nucleus caudatus and nucleus accumbens.

Morphochemical changes in brain structures in the course of chronic haloperidol treatment and the correction of these changes with tuftsin.

The systemic injection of haloperidol (4 wk, 0.5 mg/kg/d) caused the increase of protein concentration and content, and the activity level of aminopeptidase in the cytoplasm of the neurons of associated type (layer III). The nucleus of these cells decreased both in sizes and in the content of proteins. In the neurons of efferent-projectory type (layer V), the decrease of studied peculiarities as compared with control level was observed. Tuftsin (300 micrograms/kg/d) injection after chronic haloperidol treatment causes the restoring action on changed parameters in sensomotor cortex. In caudate nucleus, tuftsin influence caused further reduction of neuron's cytoplasmic area and significant reduction in protein content. The received results testify to the morphobiochemical heterogenity of investigated brain structures, which is displayed both in the case of haloperidol treatment and in the case of its correction by neuropeptide tuftsin. Chronic haloperidol administration to animals can develop a model of certain symptoms and syndromes of parkinsonism. Its most pronounced manifestation is an imbalance in the neuromediator systems, especially the dopaminergic one (Mettler and Crandall, 1959; Colls, 1984; Funk et al., 1986). The research was performed in conjunction with the physiologists, whose experiments have shown that after chronic haloperidol administration, changes in animal behavior are developed that are typical for bradikinesia, and the motor regimen of integration is disturbed (Popova and Kachalova, 1991; Dovedova and Povova, 1993). Regulatory drugs, especially the tetrapeptide tuftsin, seem to correct such disturbances.

[The morphochemical characteristics of the reaction of the motor structures of the brain to hyper- and hypofunction of the dopaminergic system]. / Morfokhimicheskie osobennosti reaktsii dvigatel'nykh struktur mozga na giper- i gipofunktsiiu dofaminergicheskoi sistemy.

The investigation of protein (aminopeptidase activity, structured proteins) and of mediator metabolism (monoaminoxidase A and B activities, acetylcholine esterase, Ca(2+)-uptake) was carried out in rat brain motor structures. The study was performed during chronic L-DOPA and haloperidol administration that is under the conditions of hyper- and hypofunction of dopaminergic system. Some peculiarities and differences of sensomotor cortex and nucleus caudatus' reactions to the dysfunction of DA system were revealed at the cellular and subcellular levels. The results show the existence of high morpho-biochemical plasticity of brain structures mentioned above.

[The effect of withdrawal from L-DOPA compounds on pathochemical changes of motor structures of the brain caused by them]. / Vliianie otmeny preparatov L-DOFA na vyzvannye imi patokhimicheskie izmeneniia dvigatel'nykh struktur mozga.

Activities of enzymes of protein metabolism (aminopeptidase, acid phosphatase), of neurotransmitters (monoamine oxidase, acetylcholinesterase) and oxidative metabolism (glutamate- and glucose-6-phosphate dehydrogenases) were studied by quantitative cytochemical procedures in brain motor structures (sensomotor cortex, caudate nucleus) as well as in brain tissues not related directly to locomotory functions (n. accumbens, hippocampus) of rats exhibiting high and low locomotory activities after repeated L-DOPA administration within 14 days as well as within 14 days after drug discontinuation. That of L-dopa (madopare) caused alterations in the enzymatic activity in the brain motor structures of rats, mainly, with a high locomotory activity. It may be suggested that madopare withdrawal-induced decreases in MAO activity might be, to a certain extent, a cause of dyskinesias occurring after discontinuation of L-DOPA drugs.

[Pathochemical changes in the motor structures of the brain under the influence of the administration of L-DOPA preparations and their withdrawal (experimental research)]. / Patokhimicheskie izmeneniia dvigatel'nykh struktur mozga pod vliianiem vvedeniia preparatov L-DOFA i ikh otmeny (éksperimental'noe issledovanie).

In the course of a long-term L-DOPA administration (14 days) and 2 weeks after its cessation the activities of some protein enzymes (aminopeptidase, acid phosphatase), neuromediator (MAO, ACE) and oxidative (glutamate dehydrogenase, glucose-6-phosphate dehydrogenase) metabolism were studied by quantitative cytochemical methods in brain motor structures (sensorimotor cortex, caudate nucleus) and in structures not directly related to motor functions (hippocampus) of rats with high and low motor activity. After L-DOPA (madapar) cessation significant changes were revealed in the formation of motor system of the brain, primarily in the group of rats with low motor activity. It is suggested that a decrease in MAO activity after madapar cessation may be responsible for dyskinesia arising after cessation of L-DOPA preparations treatment.

[The morphochemical manifestations of the chronic action of amphetamine in the brain and their correction with the delta-sleep peptide]. / Morfokhimicheskie proiavleniia khronicheskogo deistviia anfetamina v mozgu i ikh korrektsiia s pomoshch'iu peptida del'ta-sna.

Differences have been found in responses of the brain formations studied by some protein metabolic parameters. They manifest themselves both between the neurons of cortical and subcortical structures and between those of various morphofunctional types and affect the corrective action of delta-sleep peptide.