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V D Petkov

Publications and source records attributed to V D Petkov.

71 records · Page 4Linked to original sources
PubMed1987

Effect of piracetam and of standardized ginseng extract on the electroconvulsive shock-induced memory disturbances in "step-down" passive avoidance.

The effects of piracetam and standardized Ginseng extract (G115) on the memory-impairing action of electroconvulsive shock were investigated in experiments on albino rats. The changes in the memory were traced using the "step-down" conditioned reflex method of passive avoidance with negative reinforcement. Piracetam, administered in a dose of 600 mg/kg i.p. for 5 days prior to the beginning of the training sessions, completely eliminated the electroshock-induced retrograde amnesia in memory tests, as well as on the 3rd and 24th hour after the end of the training session. Standardized ginseng extract, administered in a dose of 30 mg/kg orally for 10 days prior to the beginning of the training session, markedly tended to eliminate the memory-impairing effect of electroconvulsive shock. The role of the serotoninergic neurotransmitter system for the protective effects of piracetam and of standardized ginseng extract on retrograde amnesia induced by electroconvulsive shock is investigated on the basis of earlier experiments.

Amnesia↗
PubMed1986

Effects of the ergot alkaloid elymoclavine on the level and turnover of biogenic monoamines in the rat brain.

The effect of the clavine alkaloid elymoclavine, isolated from Claviceps sp cp II, on the level and turnover of biogenic monoamines in several rat brain structures was studied. Elymoclavine administered intraperitoneally (i.p.) at a dose of 5 mg/kg significantly increased the dopamine (DA) level in the striatum and hypothalamus and enhanced the DA turnover in the striatum. A significant increase was also found in the level and turnover of noradrenaline (NA) in the hypothalamus. Elymoclavine exerted an opposite effect on the level and turnover of serotonin (5-HT) in these brain structures: the 5-HT level significantly declined and the 5-HT turnover slightly decreased in the striatum and hypothalamus. In the cerebral cortex elymoclavine significantly increased the 5-HT level. Although the stimulant effect on DA receptors appears to be a dominant element in the mechanism of action of elymoclavine, it seems that this ergot alkaloid is also characterized by a plurireceptor action. The present results suggest a certain role for the elymoclavine action on the level and turnover of brain biogenic monoamines in the mechanism of its different pharmacological effects.

Animals↗
PubMed1986

Interactions of angiotensin II and GABA-ergic agents at the threshold of convulsive reactions.

The effects of angiotensin II (AT II), GABA, muscimol (administered i.c.v.) and of amino-oxiacetic acid (AOAA) and baclofen (administered i.p.), as well as of the combinations of AT II with these substances and bicuculline, were studied with respect to the threshold of the convulsive seizures induced by timed intravenous infusion of pentylenetetrazol (PTZ) in mice. It was found in the experiments that the threshold-increasing effect of GABA, muscimol and AOAA was potentiated by AT II (applied in a dose which did not change essentially the convulsive threshold). The potentiated effect of GABA, muscimol and AOAA on the convulsive threshold, when applied in combination with AT II, was antagonized by bicuculline. The threshold-increasing effect of baclofen was not affected substantially by AT II; in this case bicuculline had no effect. On the basis of the results obtained it may be assumed that AT II performs the functions of an antocoid predominantly for the GABA-A receptors in the central nervous system.

Aminooxyacetic Acid↗
PubMed1986

Effects of meclofenoxate and Extr. Rhodiolae roseae L. on electroconvulsive shock-impaired learning and memory in rats.

In experiments on albino rats, the authors studied the effects of meclofenoxate and Extr. Rhodiolae roseae on the memory-impairing action of convulsant electroshock. "Step-down" passive avoidance training with negative reinforcement was used to trace the changes in memory. Meclofenoxate administered i.p. in a dose of 100 mg/kg body weight for five days prevented the retrograde amnesia observed after convulsant electroshock upon retention testing on the 3rd and 24th hr after the end of the training session. The Rhodiola extract administered orally in a dose of 0.10 ml/rat for 10 days, which in other experimental approaches improved learning and memory, remained ineffective here. The role of biogenic monoamines in the learning- and memory-improving effects of meclofenoxate is considered on the basis of earlier studies by the authors.

Animals↗
PubMed1986

Effects of meclofenoxate on learning and memory--dependence on the experimental conditions.

In experiments on male albino rats, it was found that meclofenoxate at a dose of 100 mg/kg i. p. applied 7 days before and 5 days during shuttle-box training did not influence learning but significantly facilitated retention (retention test was given 7 days after the end of training). With the step-through method for passive avoidance meclofenoxate at the same dose applied for 7 days improved learning and retention. In the staircase maze training with alimentary reinforcement and in the step-down passive avoidance situation, meclofenoxate at a single dose (50 mg/kg i. p.) applied before or immediately after training only tended to facilitate learning and retention, while applied at the same dose twice daily for 5 days, it significantly improved learning and retention. When meclofenoxate at a dose of 50 mg/kg i. p. was administered twice daily for 5 days in parallel with the staircase maze training, learning reached its maximum on the 5th day and remained at this level till the 10th training day even after withdrawal of meclofenoxate. In the control animals the improvement of learning progressively increased till the 10th training day. The present results suggest that the learning- and memory-facilitating effect of meclofenoxate is influenced by the training method, motivation, dose used and treatment duration.

Animals↗
PubMed1986

Effects of alcohol aqueous extract from Rhodiola rosea L. roots on learning and memory.

The effect of alcohol-aqueous extract (1:1) from Rhodiola rosea L. roots on the processes of learning and memory is studied on rats. Several methods of active avoidance with negative and positive reinforcements are used, as well as of passive avoidance. Using the maze-method with negative (punitive) reinforcement, it has been found that Rhodiola extract in a single dose of 0.10 ml per rat essentially improves learning and retention after 24 hours. Significant improvement of the long-term memory is also established in memory tests after 10-day treatment with the same dose of the extract. In the other two doses tested (0.02 and 1.0 ml per rat) the extract has no substantial effect on learning and memory. In a dose of 0.10 ml per rat the Rhodiola extract had a favourable effect on the training process using the "staircase" method with positive (food) reinforcement as well. With the other methods used (active avoidance method with negative reinforcement "shuttle-box" and passive avoidance methods "step down" and "step through") Rhodiola extract in the dose used (0.10 ml per rat) had no substantial effect on learning and memory (a certain deterioration of the training process was even observed using the "shuttle-box" method, while the "step-down" method resulted in deterioration of the memory). The great significance of the method used for studying the effects of the pharmacological agents on learning and memory for the results obtained is evident.

Administration, Oral↗
PubMed1986

Comparative studies on the central effects of angiotensin II and of its fragments.

Comparative studies were carried out of the central effects of the octapeptide angiotensin II (AT II) and of its fragments: C-terminal hexapeptide (AT 3-8), middle tetrapeptide (AT 3-6) and initial tripeptide (AT 1-3). The experiments were carried out with respect to the cerebral level of the biogenic amines DA, NA, 5-HT and their metabolites HVA and 5-HIAA in intact mice and in mice pretreated with haloperidol, as well as with respect to the animals' behaviour (haloperidol catalepsy, apomorphine stereotypy, unconditioned jumping reaction, hexobarbital sleep and the threshold of convulsive seizures induced by times intravenous infusion of pentylenetetrazol). The fragments studied were found to manifest activity in the tests used. In some respects this activity is very similar to the activity of AT II. There are also effects which differ from those of AT II, as well as effects which are entirely opposite in some respects, which makes it possible to examine some of these substance as its potential natural antagonists. All this shows that the biological activity of AT II in the brain undergoes a number of qualitative and quantitative changes when its molecule broken to produce peptides with shorter chains. In the effects observed AT II and its fragments interact predominantly with the DA-ergic transmission in the brain.

Angiotensin II↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1984

Central effects of angiotensin II, its fragment and analogues.

The effects of the octapeptide angiotensin II (AT II), its fragment Ile8 AT3-8 and the analogues Sar1 Ala8 AT II, Ala8 AT II and Ile8 AT II were studied with respect to: the level of biogenic amines (DA, 5-HT and their metabolites HVA and 5-HIAA) in the forebrain; the behaviour of the animals--haloperidol catalepsy, apomorphine stereotypy, unconditioned jumping reaction (UJR), convulsive threshold. Good correlation was found between the biochemical and behavioural effects. The fragment of AT II where phenylalanine is substituted at the C-terminal by Ile reduces the haloperidol-increased content of HVA, potentiates apomorphine stereotypy and reduces catalepsy, whereas the AT II analogues (where the C-terminal phenylalanine is substituted by Ala, and the N-terminal--by Sar) potentiate the effect of haloperidol increasing the HVA content, reduce apomorphine stereotypy and potentiate catalepsy; saralasine independently applied induces brief catalepsy; AT II, its fragment and analogues inhibit UJR, in combination with amphetamine and PTZ this effect becomes deeper; the duration of hexobarbital sleep is increased. The peptides investigated increase the convulsive threshold. The results show that the hexapeptide fragment has preserved the effects of AT II, whereas in the analogues (with changed C- and N-terminals) they are changed. The results obtained may be explained with the modulating influence of AT II-receptors on the DA-ergic receptors in the brain structures with which AT II and its fragment and analogues enter in contact.

Angiotensin II↗
PubMed1984

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↗
PubMed1984

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↗
PubMedDate not supplied

Interactions between angiotensin II, GABA and diazepam in convulsive seizures.

In experiments on male mice, we studied the effects of gamma-aminobutyric acid (GABA), angiotensin II (AT II), administered intracerebroventricularly, diazepam, injected intraperitoneally, and combinations of GABA + AT II and diazepam + AT II on convulsive seizures induced by pentylenetetrazol (PTZ) (80 mg/kg subcutaneously) and 3-mercaptopropionic acid (3-MPA) (40 mg/kg intraperitoneally). The anticonvulsant effects of GABA and diazepam on PTZ-induced seizures were increased by AT II in doses which did not significantly influence seizures. AT II applied together with GABA or diazepam in ineffective doses provoked a strong anticonvulsant effect on both PTZ- and 3-MPA-induced seizures. These results indicate that the anticonvulsant effects of GABA and diazepam on PTZ- and 3-MPA-induced seizures might effectively be potentiated by the octapeptide AT II. It is suggested that AT II operates as an endocoid acting on GABA, respectively benzodiazepine recognition sites in the CNS.

3-Mercaptopropionic Acid↗
PubMedDate not supplied

Learning and memory in rats exposed pre- and postnatally to alcohol. An attempt at pharmacological control.

Using conditioned-reflex methods for active and passive avoidance with punishment reinforcement, we found pronounced memory deficits in 12-week old rats exposed perinatally to alcohol (FAS rats). Impairment of memory was observed not only with the high dose of 9 g ethanol/kg body weight (ingested with tap water in a 6% solution) to which dams were exposed during pregnancy and lactation, but also with the ten-fold lower dose of 1 g ethanol/kg body weight (0.6% ethanol). The nootropic drugs citicholine, piracetam and meclofenoxate administered orally for five days before the training session were effective in decreasing memory deficits; particularly pronounced was the effect of piracetam and meclofenoxate. The benzodiazepine tranquilizer diazepam additionally impaired learning and memory in FAS rats. It is suggested that nootropics could be used to decrease the cognitive disturbances in some humans born to alcoholic mothers.

Animals↗
PubMedDate not supplied

[Effect of 7-hydroxygluacine on brain biogenic monoamines].

In experiments on male albino rats it was established that the aporphine alkaloid 7-hydroxyglaucine injected i.p. at a dose of 1/10 of the LD50 induced many changes in the brain level of biogenic amines. Serotonin content was significantly increased in all brain structures studied (whole brain. cortex, striatum, and hypothalamus) Dopamine level was increased in the whole brain and cortex and was decreased in the hypothalamus; noradrenaline level was increased in the cortex and was decreased in the whole brain and hypothalamus. These effects are thought to be due to the 7-hydroxyglaucine-facilitated transport of amino acids, precursors of biogenic amines, and to neurotransmitter interactions in the different brain structures.

Animals↗
PubMedDate not supplied

Effect of dotarizine on electroconvulsive shock or pentylenetetrazol-induced amnesia and on seizure reactivity in rats.

Dotarizine (DOT), a compound performing both as calcium antagonist and as 5-HT2 receptor antagonist, was evaluated for its ability to protect against electroconvulsive shock (ECS)- and pentylenetetrazol (PTZ)-induced performance deficit in a passive avoidance "step-down" task in rats. Its effect on electric and PTZ seizure models was also studied. DOT administered orally at a dose of 50 mg/kg for 5 days before learning had no significant effect on retention tests given 3 h, 24 h and 7 days after the training session. It should be noted, however, that DOT completely prevented ECS- and PTZ-induced amnesia in passive avoidance situation. DOT had a pronounced protective effect against electric seizures but did not affect PTZ seizures. The present results provide additional evidence for the role of serotonergic neurotransmitter system and calcium homeostasis for memory and seizure reactivity and may be important in the development of effective treatment strategies for memory dysfunction.

Administration, Oral↗