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T Grahovska

Publications and source records attributed to T Grahovska.

7 recordsLinked to original sources

Effects of meclofenoxate on the level and turnover of biogenic monoamines in the rat brain.

The level and turnover of biogenic monoamines in some rat brain structures were determined after treatment with meclofenoxate at a dose of 50 mg/kg administered i.p. two times a day (9 a.m. and 5 p.m.) for 5 days. Meclofenoxate decreased dopamine (DA) turnover in the frontal cortex and striatum and highly increased it in the hypothalamus. The DA level significantly declined in the striatum, tended to decline in the cortex and significantly rose in the hypothalamus. The noradrenaline (NA) turnover and level in the cortex and striatum were decreased. Meclofenoxate decreased serotonin (5-HT) turnover in the cortex, striatum and hypothalamus and increased it in the pons. At the same time, the 5-HT level rose in the cortex, striatum and pons and declined in the hypothalamus. These results suggest the neurochemical basis of the psychotropic and neuroendocrine effects of meclofenoxate.

Animals↗

Ontogenetic development of the monoamine oxidase activity and of the metabolism of biogenic monoamines in rat brain.

The article examines the ontogenetic development of the monoamine oxidase activity and of the metabolism of the dopamine, noradrenaline and serotonin in the brain of newborn, 10-day-, 20-day- and 2-month-old rats. Monoamine oxidase activity is determined using three substrates: tyramine, serotonin and beta-phenylethylamine. Monoamine oxidase A (substrate serotonin) and the total monoamine oxidase activity (substrate tyramine) are found to manifest identical development, their activity increasing quickly after birth, to reach constant values after the 10th day. The general course of the development during the first ten postnatal days shows that the post partum increase in the total monoamine oxidase activity in rat brain is predominantly due to monoamine oxidase A. Monoamine oxidase B (substrate beta-phenylethylamine) develops after the 10th postnatal day. Evidently monoamine oxidase A plays a decisive role for controlling the level of the biogenic monoamines in the young organism during the first days of the ontogenesis. Investigation of the changes in the content of dopamine, noradrenaline and serotonin in the age groups of the experimental animals chosen reveals a rapid increase in the dopamine and noradrenaline levels even during the first ten days of the ontogenesis. The increased total monoamine oxidase activity and the increased dopamine content correspond to its increased turnover rate during ontogenesis. The turnover rate of noradrenaline remains unchanged between the 10th and 20th postnatal days. The increasing serotonin level between the 20th and 60th post partum days corresponds to its increased turnover rate.

Aging↗

Enkephalin receptor changes in rat brain during aging.

In experiments on 2-, 10- and 22-month-old rats, it was found that the number (Bmax) of brain enkephalin (Enk) receptors decreased with aging. The Bmax values in the cortex of 22-month-old rats decreased by 57%, in the striatum by 33% and in the hypothalamus by 84% as compared to those in 2-month-old rats. The Enk receptor sensitivity in the brain of aged rats also decreased (increased Kd). It is suggested that the changes in opiate receptors play a role in the age-related reduction of the adaptive capacity of the organism. The studies with repeated administration of L-dopa or haloperidol provided further evidence for interactions between opiate and dopaminergic systems.

Aging↗

Changes in rat liver and brain monoamine oxidase activity after acute treatment with some heavy metal salts.

In in vivo and in vitro experiments the effects of some heavy metal salts (Cu, Co, Cd, Pb, Ni, Zn, Hg, As, Bi and Sn) on rat liver and brain mitochondrial monoamine oxidase (MAO) activity was studied using three different substrates (tyramine, 5-hydroxytryptamine (5-HT) and beta-phenylethylamine (2-PEA). It was established that some of the metals (Cu, Cd, Bi) inhibited MAO activity both in vivo and in vitro experiments, others like Ni, Zn, As and Sn inhibited it only in vivo while Hg exerted inhibitory action only in vitro. The in vivo experiments showed significantly higher sensitivity of brain MAO as compared with liver MAO to the inhibitory action of metals. The same higher susceptibility was shown by liver and brain MAO-A form. It was concluded that the inhibitory effects of some heavy metal salts on MAO activity were not directly connected with their action on enzyme thiol groups but more probably with changes in the enzyme membrane surroundings in the different organs.

Animals↗

Age-related changes in rat brain dopaminergic receptors.

The number (Bmax) and affinity (Kd) of [3H] spiroperidol binding sites in the cerebral cortex, striatum and hypothalamus of 2-, 10- and 22-month old male Wistar rats (20 rats per group) injected i. p. for 10 days with saline, L-DOPA (250 mg/kg) or haloperidol (1 mg/kg) were determined in the presence of 10(-6) M unlabelled haloperidol. The Bmax values in the three brain structures studied decreased with aging in both controls and L-DOPA- or haloperidol-treated rats. The Kd values increased with age. That specific [3H] spiroperidol binding was determined through displacement of the labelled ligand by haloperidol suggested that an age-related loss of dopamine receptors occurred in the brain structures studied. However, considering the fact that in the cerebral cortex [3H] spiroperidol labels a subclass of serotonin receptors (5-HT2) rather than DA receptors, the present results, particularly those concerning the cerebral cortex, suggest an age-related decrease also in the number of 5-HT receptors in this cerebral structure.

Age Factors↗

Changes in the brain biogenic monoamines of rats, induced by piracetam and aniracetam.

Single oral dose of 600 mg/kg weight piracetam, respectively 50 mg/kg aniracetam, causes essential changes in the level and turnover of dopamine (DA) and serotonin (5-HT) in some rat cerebral structures. When the animals were killed one hour after the administration of the drugs, piracetam significantly increased the DA level in the cerebral cortex and in the striatum, as well as the 5-HT level in the cortex, reducing the 5-HT level in the striatum, brain stem and hypothalamus. At the same time, under the effect of piracetam the DA turnover was accelerated in the cortex and hypothalamus and delayed in the striatum, the noradrenaline turnover was accelerated in the brain stem, the 5-HT turnover was accelerated in the cortex and delayed in the striatum, stem and hypothalamus. Under the effect of aniracetam the DA level was reduced in the striatum and hypothalamus; the 5-HT level was also decreased in the hypothalamus and increased in the cortex and striatum. Aniracetam delayed the DA turnover in the striatum and the 5-HT turnover in the hypothalamus, accelerating the 5-HT turnover in the cortex, striatum and stem. The results obtained show that the changes induced in the cerebral biogenic monoamines participate in the mechanism of action of piracetam and aniracetam, whereby it seems that the analogies and differences in their effects on the cerebral biogenic monoamines play a definite role for the observed analogies and differences in the behavioural effects of these two "nootropic" compounds.

Animals↗

A rapid and sensitive assay for monoamine oxidase activity.

Based on the Berthelot reaction, a new sensitive and rapid procedure for monoamine oxidase (MAO) determination with substrate tyramine has been developed. The saturation with oxygen and the separation of ammonia from the substrate were omitted. At the end of incubation the samples were deproteinized with ethanol and consecutive centrifugation. The newly-formed ammonia is converted into the coloured compound indophenol, using the procedure of Fenton (1962). The indophenol concentration, respectively NH3 is determined by spectrophotometry at 625 nm, and calculated by comparison with a set of standard amounts of NH3. The enzyme activity is expressed as nanomoles ammonia, formed by 1 mg protein for 1 min. The method was tested for studying the relationship between the enzyme activity, time of incubation and protein concentration, as well as the effect of pargyline. The kinetics of MAO, using both liver and brain mitochondria as enzyme material was also studied. Considering the specificity, simplicity, versatility and rapid performance, the new method showed several advantages in comparison with the other known methods for MAO determination.

Animals↗