Biomedical subjects

V D Petkov

Publications and source records attributed to V D Petkov.

At least 37 records · Page 2Linked to original sources

PubMed1992

Effect of CDP-choline on learning and memory processes in rodents.

The effects of cytidine (5') diphosphocholine (CDP-choline) on learning and memory were studied using conditioned reflex methods for passive avoidance and active avoidance with punishment reinforcement (step-through, step-down, shuttle box and maze), for active avoidance with alimentary reinforcement (staircase maze), and the Morris water maze. The majority of experiments involved comparative studies of the nootropic drugs meclofenoxate and/or piracetam. CDP-choline was administered orally, in some of the experiments also intraperitoneally, at doses of 10-500 mg/kg body weight once or twice daily for 5 or 7 days. In separate cases only single doses were administered. Trainings started one hour after the last dose of the drugs. Retention tests were given 3 h, 24 h, 7 days or 10 days after training. The results obtained with the different methods document CDP-choline's ability to improve learning and memory in rats and mice. No essential differences in the effects of CDP-choline were established upon oral and intraperitoneal administration of the drug. The learning- and memory-facilitating effects of CDP-choline were similar to those of meclofenoxate and piracetam. The results of the present study permit us to define CDP-choline as a substance capable of improving cognitive levels.

Animals↗

PubMed1991

Age-related changes of the effects of a group of nootropic drugs on the content of rat brain biogenic monoamines.

1. The changes in the levels of brain biogenic monoamines (BMAs) after chronic (7 days) treatment with piracetam, aniracetam and structural analogues of aniracetam (p-H, p-F, p-Cl, p-P and m-D) were studied in young and old rats. 2. An age-related significant decrease in the BMA content was established in old rats. 3. Most of the investigated compounds increased the level of one or other BMA in one or other of the brain structures studied. This elevation was predominantly established in old rats. 4. The present results and those from previous behaviour studies show that elevation of one or more of the BMA levels in one or more brain regions plays a beneficial role in the realization of their effects on the processes of learning and memory.

Aging↗

PubMed1991

Memory impairment induced by combined disturbance of noradrenergic and dopaminergic neurotransmissions: effects of nootropic drugs.

The effect of the combined application of the alpha 2-adrenoreceptor agonist clonidine and of the dopaminergic blocker haloperidol on the memory processes was tested on albino rats. The changes in the memory were studied using the following methods: two-way active avoidance with negative reinforcement (shuttle-box) and passive avoidance (step-through). Both clonidine (0.05 mg/kg) and haloperidol (0.5 mg/kg), injected intraperitoneally immediately after the end of the training session, slightly impaired retention in the memory tests used with both training methods. Their combined application, however, caused a marked amnesia. This amnesia model was used to study the effects of the nootropic drugs: adafenoxate and the newly-synthesized compound benzoyl-1, 4-dipyrolydinone (p-P). Administered orally in a dose of 100 mg/kg for 5 days prior to the training session, both adafenoxate and p-P fully eliminate the amnesia caused by the combined application of clonidine and haloperidol. The paper discusses the role of the noradrenergic and dopaminergic neurotransmitter systems for the amnestic effect of the clonidine + haloperidol combination, as well as for the favourable effect on the cognitive functions of the tested nootropic drugs adafenoxate and p-p.

Animals↗

PubMed1991

Changes in brain muscarinic and beta-adrenoreceptors of the offspring of ethanol-consuming mothers (experiments on rats).

The muscarinic cholinoreceptors in the cerebral cortex, striatum, hippocampus and hypothalamus were studied in a group of 12-week-old rats subjected to the effect of alcohol in utero and during the lactation period. The beta-adrenoreceptors in the same brain regions were investigated in another group of 8-week-old rats, likewise exposed perinatally to ethanol. The affinity of the muscarinic receptors was found to decrease in the hippocampus of the rats perinatally exposed to ethanol (increase of the Kd-value), and of the beta-adrenoreceptors to increase (decrease of the Kd-value) compared with the affinity of the respective receptors in the same brain structure of the control group of rats of the same age. The role of the changes induced by ethanol during the perinatal development in the muscarinic and beta-adrenoreceptors in the hippocampus, and especially the disturbed balance between these receptors, is examined as one of the factors responsible for the cognitive disturbances inherent to the rats with foetal alcohol syndrome.

Animals↗

PubMed1991

Modulation of the effects on learning and memory of nootropic drugs and central stimulants when applied together.

In experiments on rats using passive avoidance with punishment reinforcement (step-through) and two-way active avoidance with punishment reinforcement (shuttle-box), we examined the effects on acquisition and retention of different combinations of the nootropic drugs meclofenoxate (Mf), citicholine (CCh), piracetam (Pc), the structural analogues of aniracetam p-P and p-F, standardized extract from ginseng roots (PG) and the psychostimulants caffeine (Caf) and amphetamine (Amph). Favorable effects (more pronounced improvement of learning and/or memory as compared to that caused by the drugs when given alone) were in some cases obtained by the combination Mf+Caf, Pc+Caf, CCh+Caf, p-F+Caf, Mf+CCh, as well as by the combination Mf+PG applied to rats with electroconvulsive shock-induced amnesia. However, in some cases the combined administration of two drugs with favorable effects on memory did not led to summation or potentiation but rather to disappearance of these effects. This was observed under certain experimental conditions with some combinations of Caf and CCh, Mf, Pc and p-P and with some combinations of Amph and Mf. Based on our earlier results and data in the literature, we present some considerations about the role of the neurotransmitter mechanisms of action of the drugs tested as neurochemical correlates of their effects on memory. It is suggested that the unfavorable results obtained in some cases with combinations of nootropics and psychostimulants are due to the possible disturbance of selective acquisition by the psychostimulant drug.

Amphetamine↗

PubMed1991

Effects of serotoninergic receptor antagonists and their combination with scopolamine on memory.

Using the method for passive avoidance with punishment reinforcement (step-down), it was found that the serotonin (5-HT)-receptor blockers methergoline, methysergide and ritanserin at a dose of 5 mg/kg b.w. administered i.p. 30 min before the training session as well as the M-cholinergic-receptor blocker scopolamine administered at a dose of 2 mg/kg b.w. 90 min before training impaired acquisition and retention of memory traces. The memory impairment was also manifested by the poor habituation of methergoline- and scopolamine-treated rats placed in an unfamiliar environment. Memory deficit was increased by the combination of methergoline or ritanserin with scopolamine. On multiple administration before training the nootropic drug adafenoxate completely prevented the amnestic effect of the combination methergoline plus scopolamine.

Animals↗

PubMed1991

Memory effects of a group of newly-synthesized pyrrolidine derivatives with putative nootropic effect.

The original pyrrolidine derivatives with putative nootropic effect: para-chloro-phenoxyacetyl-2-pyrrolidinone (Mf-P), 1-adamantanyl-2-pyrrolidinone (A-P), 2-oxo-1-pyrrolidine-3,7-dimethylxanthine (A-T) and para-benzoyl-1,4-dipyrrolidinone (p-P), were studied. Toxicological screening performed on mice demonstrated the low toxicity of the compounds. Five- or seven-day oral administration of the substances to rats in a dose of 100 mg/kg weight facilitated the learning process and improved the memory of the rats with most of the conditioned-reflex methods used. Application of Mf-P to 2- and 24-month-old rats for 8 days induced changes in the levels of some biogenic monoamines in the brain structures studied. The results obtained, as well as the results of other studies in this laboratory, show that the pyrrolidine derivatives studied, which can be considered to be original new aniracetam analogues, improve the memory process. This effect varies strongly depending on the regime of application of the compounds studied, on the memory capacity of the experimental animals and on the experimental method used. The changes in the brain neurotransmission induced by the substances studied play an essential role in their mechanism of action.

Animals↗

PubMed1991

Comparative studies on the influence of ONK (N(5-hydroxynicotinoil) glutamic acid), piracetam and meclofenoxate on the learning- and memory-impairing effect of scopolamine, clonidine, and methergoline.

The effects of the new compound N(5-hydroxynicotinoil)glutamic acid (ONK) in comparison with the well-known nootropic drugs piracetam and meclofenoxate on cognitive functions impaired by scopolamine, clonidine or methergoline were examined in albino rats and mice. The changes in learning and memory were studied by the two-way active avoidance "shuttle-box", passive avoidance "step-down" in rats and passive avoidance "step-through" in mice. The present results showed that ONK (50 mg/kg) injected intraperitoneally (i. p.), piracetam (800 mg/kg) and meclofenoxate (100 mg/kg) administered orally once daily for 5 days before training completely antagonized the scopolamine-provoked amnesia in step-through-trained mice. ONK (50 mg/kg) administered i. p., piracetam (600 mg/kg) and meclofenoxate (100 mg/kg) administered orally once daily for 5 days before training abolished the memory-impairing effect of clonidine in shuttle-box-trained rats and the amnestic effect of methergoline in step-down trained rats. The observed antiamnestic effects of the nootropic drugs studied are probably realised through their influence on cholinergic, noradrenergic and serotoninergic neurotransmission. The favourable effect of ONK on cognition might be of interest for therapeutic practice.

Animals↗

PubMed1990

Effect of the combination of the benzodiazepine tranquilizer medazepam and the nootropic agent meclofenoxate on the activity of rat brain muscarinic receptors.

1. The effect of 7-day treatment with the benzodiazepine tranquilizer medazepam (5 mg/kg), the nootropic agent meclofenoxate (100 mg/kg) and their combination in the same doses on the binding activity of muscarinic receptors in four rat brain structures (cerebral cortex, striatum, hippocampus and hypothalamus) were studied using the antagonist [3H]-1-quinuclidinyl benzylate [( 3H]-QNB) as radio-ligand. 2. Medazepam treatment caused significant decrease of muscarinic receptor binding affinity (Kd) and of the receptor binding capacity (Bmax) in the brain structures studied. The number of muscarinic binding sites was unsignificantly decreased only in the hippocampus. 3. Meclofenoxate treatment caused an increase of muscarinic receptor affinity and a decrease of the binding capacity in the cerebral cortex and hypothalamus and an increase of the binding affinity in the striatum and hippocampus. 4. The combination of medazepam and meclofenoxate caused no significant changes of both muscarinic receptor characteristics in the hippocampus and of the receptor affinity in the striatum and hypothalamus in comparison with control rats. The Bmax values were decreased in the cerebral cortex, striatum and hypothalamus when compared with control animals. The differences observed were slighter than those determined after the comparison of medazepam treated rats with control rats. 5. The results obtained afford an opportunity to suggest that the nootropic agent meclofenoxate acts to moderate the effect of the benzodiazepine tranquilizer medazepam on the activity of rat brain muscarinic receptors.

Animals↗

PubMed1990

Changes in brain biogenic monoamines induced by the nootropic drugs adafenoxate and meclofenoxate and by citicholine (experiments on rats).

1. The effects of Adafenoxate (Adf), meclofenoxate (Mf) and citicholine (CCh) administered at a daily dose of 100 mg/kg for 7 days on the levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the frontal cerebral cortex, striatum, hippocampus and hypothalamus of rats were studied. 2. Adafenoxate increased the NA level in the striatum and decreased it in the hypothalamus; it increased the DA level in the cerebral cortex and hypothalamus and decreased it in the striatum; it increased the 5-HT level in the cerebral cortex and decreased it in the hippocampus. 3. Meclofenoxate decreased the NA level in the cerebral cortex and hypothalamus; it increased the DA level in the hippocampus and hypothalamus and the 5-HT level in the cerebral cortex, striatum, hippocampus and hypothalamus. 4. Citicholine increased the NA level in the cerebral cortex and hypothalamus; it increased the DA level in the striatum and the 5-HT level in the cerebral cortex, striatum and hippocampus. 5. An attempt is made to explain some similarities and differences in the behavioral effects of the drugs tested (and those observed in other studies) by the changes they induce in brain biogenic monoamines.

Animals↗

PubMed1990

Immunomodulating activity of ginsenoside Rg1 from Panax ginseng.

The immunomodulatory activity of ginsenoside Rg1 from Panax ginseng was studied in mice using sheep red cells as the antigen. It was found that ginsenoside Rg1 at a dose of 10 mg/kg administered for three consecutive days before immunization increased the number of spleen plaque-forming cell, the titers of sera hemagglutinins as well as the number of antigen-reactive T-cells. Ginsenoside Rg1 also increased the number of T-helper cells with respect to the whole T-cell number and the splenocyte natural killer activity. Ginsenoside Rg1 induced an augmentation of the production of IL-1 by macrophages and exerted a direct mitogenic effect on microcultured thymus cells. Ginsenoside Rg1 also partly restored the impaired immune reactivity by cyclophosphamide treatment.

Animals↗

PubMed1990

Effects of nootropic agents on the performing of active two-way avoidance tasks in young and old rats.

Experiments were made on 2- and 18-month-old male rats to test the effects on the acquisition and retention of piracetam, meclofenoxate and four newly-synthesized substances with assumed nootropic action: pyrrolidine derivatives with code names p-F, p-P and A-T, as well as the derivative of para-chlorophenoxypropionic acid, with code name 4-Cl-alpha PA. The method of two-way active avoidance was used, with punishment reinforcement during 5-day training and retention tests on the 14th day after the beginning of training. The agents studied were applied orally in doses of 30 and 150 mg/kg for 3 days (2 days before training and on the first day of training) and then again one hour before the retention testing. The older rats manifested a poorer learning capacity than the younger ones. Piracetam produced the best effect both on learning and on retention. Compounds with code names p-F, p-P and A-T induced an increase in the number of avoidances compared with the controls on isolated days only, according to the tests for acquisition. The favourable effects observed are not in close dependence either on the dose applied, or on the age of the experimental animal. No significant effects were observed under the effect of meclofenoxate and of its structural analogue 4-Cl-alpha PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1990

Changes in the synapses in the parietal cortex of senescent rats.

Quantitative parameters characterizing the density of the synapses, the pre- and postsynaptic elements, and the synaptic contact zones (SCZ) in the parietal cortex of young adult (3-month-old) and aged rats (24 months) were investigated using an automated computer system. A big loss of axospinous, but not of axodendritic synapses, was observed in the aged rats. The parameters for the synaptic vesicles and SCZ were changed also only in the axospinous synapses. The changes in the quantitative parameters are accompanied by changes in the structure of synapses. The structural changes may be considered as being degenerative and regenerative.

Aging↗

PubMed1990

Study of the effects of nootropic agents on the adrenergic neurotransmission in smooth muscles of young and old animals.

The effects of compounds from the group of nootropic agents on the peripheral adrenergic neurotransmission in animals of different ages were studied in in vitro experiments. The experiments were performed on smooth muscle preparations isolated from young sexually mature (4-5-month-old) and old (22 month-old) rats treated twice daily for 7 days with 50 mg/kg of the nootropic agents piracetam, its structural analogues p-H and p-Cl, aniracetam and Ginseng extract. The animals were decapitated on the 7th day, the changes in the contractile responses of the smooth muscles to noradrenaline (NA) or electrical stimulation (ES) were studied in isolated preparations from vas deferens, aorta and anococcygeal muscle. The results show that the compounds studied can modulate the contractile effects of NA and ES, their action being most often potentiating and more pronounced in the smooth muscles manifesting weaker responses. In some cases the reactivity of the smooth muscle preparations to the stimuli applied was reduced after the nootropic agents. These effects can be partly explained with changes in the sensitivity of the pre- and postsynaptic alpha-adrenergic receptors. The possible variabilities in the influence on the two receptor populations in the different smooth muscles could explain the differences in the observed modulatory effects of the nootropic agents. The data obtained show that in prolonged therapeutic application of nootropic agents it is necessary to bear also in mind their possible influence on the peripheral neurotransmitter systems.

Aging↗

PubMed1990

Age-related differences in memory and in the memory effects of nootropic drugs.

In experiments of 2-, 5-, 10- and 22-month old rats, using active avoidance with punishment reinforcement (maze and shuttle-box) and passive avoidance (step-down), we found that acquisition and retention in aged rats were impaired significantly or only as a trend. The nootropics adafenoxate, meclofenoxate, citicholine, aniracetam and the standardized ginseng extract administered orally for 7 to 10 days usually facilitated learning and improved memory in the rats of all ages. By some of the indices used the drugs gave more pronounced favourable effects in old rats, while by others better effects were observed in young or adult rats. The results demonstrate significant age-related differences in learning and memory in rats and in the effects of nootropic drugs on these processes.

Aging↗

PubMed1990

Effects of citicholine and of the combination citicholine + piracetam on the memory (experiments on mice).

The memory effects of citicholine (CCh) and piracetam (Pc) were tested in experiments on mice using the training method with passive avoidance and negative reinforcement (step-through). In single doses of 25, 50, 100 and 500 mg/kg, CCh applied one hour prior to training enhanced to the same degree and statistically significantly the retention of the memory traces in tests both 24 h and 7 days after the training session; Pc in a dose of 500 mg/kg improved the retention in memory tests 24 h after training, but had no significant effect during the tests 7 days after the training. Combined application of CCh and Pc in doses which are ineffective with respect to the memory process (CCh--10 mg/kg and Pc--200 mg/kg) caused a significant enhancement of the retention during the tests both 24 h and 7 days after the training. Scopolamine (2 mg/kg i.p.), applied 30 min prior to the training, manifested a marked amnestic effect during the tests 24 h after the training, but this effect was totally prevented if either CCh in a dose of 50 mg/kg or Pc in a dose of 500 mg/kg were applied before scopolamine. Citicholine in a dose of 100 mg/kg, as well as the combination of 50 mg/kg CCh and 500 mg/kg PC, not only completely prevented the scopolamine-induced amnesia, but they also significantly increased the retention of the memory traces in the scopolamine-treated mice compared with the retention observed in the control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnesia↗

PubMed1989

Age-related changes in rat brain muscarinic receptors and beta-adrenoreceptors.

1. In experiments on 2-, 10- and 22-month old rats, it was found that the Bmax values for muscarinic receptors and beta-adrenoreceptors increased in the cerebral cortex, striatum and hippocampus of 10-month old rats as compared to those in 2-month old rats. 2. The Bmax values for both receptor types significantly decreased in the same brain structures of 22-month old rats as compared to those in 10-month old rats. In the striatum and hippocampus of 22-month old rats the binding capacity decreased as compared also to those in 2-month old rats. 3. In the hypothalamus there was also a tendency towards increasing the binding capacity of 10-month old rats and towards decreasing the binding capacity of 22-month old animals only for muscarinic receptors. The beta max of beta-adrenoreceptors remained unchanged in all age groups studied. 4. The receptor affinity of both receptor types was in most cases unaltered with advancing age. The Kd values were slightly increased only in the striatum and hippocampus of 22-month old rats as compared to 10-month old rats. 5. The role of age for the changes in the activity of brain muscarinic and beta-adrenoreceptor systems is discussed.

Aging↗

PubMed1989

Memory effects of the new derivative of the p-chlorophenoxyacetic acid adafenoxate compared to the effects of some cognition-enhancing drugs in rats.

In experiments on male rats the effects of adafenoxate (Adf), meclofenoxate (Mf), piracetam (Pc) and citicholine (CCh) on learning and memory were studied using the maze active avoidance method with punishment reinforcement. The drugs tested were administered twice daily for seven days at doses of 10 and 50 mg/kg body weight for Adf, Mf and CCh and only at a dose of 50 mg/kg body weight for Pc. The effects of these drugs on scopolamine-treated and scopolamine-untreated rats were also studied using the step-through method. Retention tests were given 24 h and 7 days after the end of the training session in the punishment-reinforcement active avoidance and 3 and 24 h after training in the passive avoidance situation. With the maze method statistically significant results about the favourable effects of the four drugs were obtained by most of the indices for learning and memory. However, the effects of the drugs tested were differently pronounced depending on the dose utilized. With the step-through method all four drugs prevented the scopolamine-induced amnesia. Comparing the present results with other data previously obtained about the effects of the drugs tested and of other nootropic drugs on brain biogenic monoamines, it is suggested that induced changes in biogenic monoamines are responsible for the similarities and the differences in the effects of nootropic drugs on learning and memory.

Animals↗