Biomedical subjects

V V Petkov

Publications and source records attributed to V V Petkov.

At least 37 records · Page 2Linked to original sources

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

Caerulein receptors on the cholinergic neurons in guinea-pig ileum.

The release of [3H]ACh and the contractions of guinea-pig ileal longitudinal muscle preparations, with myenteric plexus attached were measured and recorded simultaneously. Caerulein in concentrations of 10(-11) M to 10(-8) M caused dose-dependent increase of the contractions and the [3H]ACh release. This excitatory effect of caerulein was sensitive to TTX (10(-6) M). Proglumide selectively antagonized both the contractions and the [3H]ACh-releasing effect of caerulein. Electrical field stimulation (O.1 Hz)-evoked contractions were sensitive to atropine. Caerulein (10(-9) M) did not influence the electrically-evoked release of [3H]ACh and the electrically-evoked contractions. Nifedipine (10(-6)M) decreased them about 50%. In the presence of nifedipine caerulein produced an inhibitory effect on the electrically-induced contractions. This nifedipine-unmasking inhibitory effect of caerulein was accompanied by a decrease of the [3H]ACh release and was prevented by proglumide.

Acetylcholine↗

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↗

PubMed1990

125I-insulin binding is decreased in olfactory bulbs of aged rats.

125I-insulin binding was studied in membrane preparations of olfactory bulb, frontal cortex, hippocampus and hypothalamus from mature (5-month-old) and aged (22-month-old) rats. In the young animals the highest level of specific insulin binding was found in the olfactory bulb, with lower values of specific insulin binding in the frontal cortex, hippocampus and hypothalamus. In the aged rats the specific insulin binding was not changed in the frontal cortex, hippocampus and hypothalamus as compared to the young ones. A significant decrease of total insulin binding was observed only in the olfactory bulbs of aged rats (0.67 +/- 0.04 pmol insulin/mg protein) as compared to the mature animals (1.3 +/- 0.08 pmol insulin/mg protein). Scatchard analysis of insulin binding data revealed that this decrease was due to changes in the number of binding sites rather than to changes in the affinity of insulin receptors. It was suggested that the decrease observed in insulin receptor number in olfactory bulbs of aged rats might be due to the atrophic changes in the structure of olfactory bulbs previously shown by electron microscopy for aged rats.

Aging↗

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

Changes in 5-HT1 receptors in different brain structures of rats with isolation syndrome.

1. Prolonged (3 month) individual housing of Wistar rats produced aggressive muricidal behavior in 28% of the animals. 2. Binding studies with [3H]5-HT showed that the affinity (Kd) of 5-HT1 receptors in the frontal cortex, striatum, hippocampus and hypothalamus of isolated aggressive rats was significantly decreased as compared to that in grouped rats. 3. The affinity of 5-HT1 receptors was also significantly decreased in the striatum, hippocampus and hypothalamus of isolated nonaggressive rats. 4. The number (Bmax) of 5-HT1 receptors was significantly decreased in the hippocampus and hypothalamus of isolated aggressive rats and in isolated nonaggressive rats it was decreased only in the hypothalamus. 5. The data suggest that aggressive muricidal behavior in rats with syndrome of social isolation is connected with the decreased activity of brain 5-HT1 receptors.

Aggression↗

PubMed1990

4-Aminopyridine activates an inhibitory alpha 1-adrenergic mechanism unmasked by nifedipin on the electrically stimulated rat vas deferens.

4-Aminopyridine (4-AP) acts by blocking voltage dependent potassium channels in excitable membrane thus increasing the influx of extracellular (Ca2+) in response to an action potential. 4-AP exerts either in vivo or in vitro effects in many organs. The present report deals with a study on the electrically stimulated rat vas deferens of the action of 4-AP on Ca2+ mediated mechanism related to the adrenergic transmission. To avoid the interference of the non-adrenergic components we used the epididymal portion of the vas. 4-AP was shown to enhance the electrically-stimulated contractions in a way which was inversely related to external Ca2+. This effect was abolished by nifedipine (1 x 10(-6) M). Unexpectedly, however, 4-AP acted synergistically with nifedipine by enhancing the inhibition of the electrically-induced tension sustained by nifedipine. This property of 4-AP was shared by noradrenaline, phenylephrine, clonidine, serotonin, morphine and ATP. Their inhibitory effects were antagonized by prazosin (1 x 10(-8) M), yohimbine (2.5 x 10(-5) M), methysergide (1 x 10(-4) M), naloxone (1.2 x 10(-7) M), and theophylline (6 x 10(-6) M) respectively. The inhibitory effect of 4-AP was antagonized only by prazosin (1 x 10(-8) M) and was not observed in vas deferens of rats pretreated with reserpine. It is concluded that 4-AP is able not only to activate excitatory mechanisms but also to stimulate inhibitory alpha 1-adrenergic mechanisms.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

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

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

Effect of diazepam and medazepam on pentylenetetrazol kindling in albino rats.

Experiments on male albino rats were carried out in order to study the effects of diazepam and medazepam on the clonic-tonic convulsions in kindling phenomena evoked by multiple injections of a subconvulsive dose (40 mg/kg) pentylenetetrazol (PTZ). In the two doses used, both diazepam (0.25 and 1.0 mg/kg) and medazepam (2.0 and 5.0 mg/kg) manifest a marked anticonvulsive effect on the clonic-tonic convulsions in PTZ-kindled rats, with a marked dose-effect dependence. The evidence in the literature that the hippocampus plays the role of a pathologically determining structure in the realization of the PTZ kindling and that neurotransmission in the inhibitory synapses in the hippocampus is achieved by gamma-aminobutyric acid (GABA), gives grounds to accept that the anticonvulsive effects of diazepam and medazepam, observed in PTZ kindling, occur through GABA-ergic mechanisms, because the facilitating effect of benzodiazepines on the GABA-ergic neurotransmission is well known.

Animals↗

PubMed1989

Age-determined changes in the effects of a newly synthetized cholinesterase inhibitor on exploratory behavior, memory and striatal cholinesterase activity in rats.

The newly synthetized cholinesterase inhibitor C-8 (a structural analogue of physostigmine) at a dose of 4 mg.kg-1 exerted no inhibitory effect on the spontaneous locomotor activity in 2-, 10- and 22-month old male Wistar rats. Upon open field test, C-8 facilitated the process of habituation in the rats of all three groups. In a passive avoidance situation (step-down and step-through) C-8 had a favorable effect on the memory of 22-month old rats mainly. C-8 inhibited the cholinesterase activity in the striatum of 2-month old rats by 29%, in 10-month old rats by 73%, and in 22-month old rats by 30%.

Aging↗

PubMed1989

Changes in the synapses of rat hippocampus following pre- and postnatal alcohol exposure.

Quantitative and qualitative changes in the synapses in stratum lacunosum-moleculare of rat hippocampus following pre- and postnatal alcohol exposure were studied. Dense and lamellar bodies, damaged mitochondria, autophagic vacuoles and dilatated cisterns of the smooth endoplasmic reticulum were seen in axons and dendrites. The enlarged glial processes were also found. The area and the vesicle number of presynaptic terminals were decreased in CA1 and CA3 hippocampal fields, while the vesicle number per area of synaptic contact zones (SCZ) was decreased only in field CA3. The relative and absolute lengths of the SCZ, the total length and total surface of the SCZ were quite differently changed in both fields. The synaptic density was insignificantly increased. The synaptic changes are thought to be due to the impaired development of the pyramidal cell dendrites in the hippocampus and their afferents.

Abnormalities, Drug-Induced↗

PubMed1989

Biological tests for opiate activity of newly-synthesized compounds--opioid peptides and cyclic beta-diketones.

A group of newly-synthesized (Leu5) enkephalinamides and their derivatives, with incorporated D-amino acids, as well as a group of cyclic beta-diketones from the group of 1, 3-indandiones, were partially pharmacologically characterized in experiments in vivo and in vitro. The substances studied, applied subcutaneously in doses of 50 to 1250 micrograms/kg bogy mass in mice, did not induce symptoms of acute and late toxicity. According to the parameters of the neuropharmacological screening tests performed, no significant differences were observed between the mice treated with the agents tested and the control mice. All five agents investigated significantly shortened the duration of hexobaribital-induced sleep. In the experiments using the conflict test after Vogel et al. (1971), (D-Ala2, D-Leu5) enkephalinamide induced a behavioural effect which can be qualified as anxiolytic. The same analogue also manifested a marked analgesic effect with the two tests used: hot plate test and the peritoneal test with glacial acetic acid. The cyclic beta-diketones-(methindiones) tested also manifested good analgesic effect with both test. (D-Ala2, D-Leu5), enkephalinamide strongly reduced the electrically induced contractile responses of the ileum. This effect was completely prevented by naloxone. The fact that (D-Ala2, D-Leu5) enkephalinamaide, known as a selective agonist of the delta-opiate receptors, proved to be particularly active suggests that both mu- and delta-type opiate receptors exist in the guinea-pig ileum. The pronounced analgesic effect of the leucine-enkephalinamide analogue with two substituted D-amino acids and of the two cyclic beta-diketone methindiones opens up new possibilities for synthesizing efficient analgesic agents.

Analgesics↗

PubMed1989

Changes in the serotonin, dopamine and noradrenaline levels in the cerebral cortex of rats trained for active and passive avoidance.

Male Wistar rats were trained for active (shuttle-box) and passive (step-down) conditioned avoidance through negative reinforcement. The memory tests carried out on the 24th hour and on the 7th day after the training revealed that the rats trained for active avoidance demonstrated a considerably higher number of avoidance in both tests, compared with the avoidance shown during the training session. The memory tests on the 24th hour and on the 7th day after training for passive avoidance showed that the rats had mastered the task lastingly. The levels of serotonin (5-HT), dopamine (DA) and noradrenaline (NA) in the frontal cortex were determined on the 24th hour and on the 7th day after the training, both for active and for passive avoidance. The 5-HT content was considerably increased on the 24th hour after both active and passive avoidance training, whereas on the 7th day its level was unchanged for both types of training. The DA content was slightly increased on the 24th hour and on the 7th day after active avoidance training, though it was considerably reduced on the 24th hour after passive training. The NA level was insignificantly raised on the 24th hour after active avoidance training, being considerably reduced after passive avoidance training. The observed changes in the cortical levels of 5-HT, DA and NA are probably caused to a certain extent by the different stressors used as unconditioned-reflex stimuli during the training for active or passive avoidance.

Animals↗

PubMed1988

The effect of chronic diazepam and medazepam treatment on the number and affinity of muscarinic receptors in different rat brain structures.

1. The effect of chronic (19-day) treatment with the benzodiazepine tranquilizers diazepam (1 mg/kg/day, i.p.) and medazepam (5 mg/kg/day, i.p.) on the binding characteristics of muscarinic receptors in four rat brain structures: cerebral cortex, striatum, hippocampus and hypothalamus were studied using [3H]l-quinuclidinyl benzylate ([3H]QNB) as radioligand. 2. Diazepam and medazepam treatment caused an overall decrease in muscarinic receptor binding affinity (Kd). 3. The number (Bmax) of muscarinic receptors declined in the hippocampus and striatum and rose in the hypothalamus after both benzodiazepines. The Bmax of muscarinic receptors in the cerebral cortex was increased after diazepam treatment. 4. The changes in the binding characteristics of muscarinic receptors might be due to benzodiazepine-induced occurrence of two populations of muscarinic binding sites: P1 (high affinity, low capacity) and P2 (low affinity, high capacity). 5. The altered brain muscarinic receptor functions after chronic diazepam- or medazepam treatment suggest the role of cholinergic neurotransmission in the mechanism of action of benzodiazepines.

Animals↗

PubMed1988

Age-related changes in brain neurotransmission.

In experiments on 2-, 10- and 22-month-old rats it was found that the Bmax values of dopamine (DA2), serotonin (5-HT1) and enkephalin (Enk) receptors as well as the 5-HT level in the three brain regions (cortex, striatum and hypothalamus) decreased with age; the DA level in the brain cortex and striatum and the noradrenaline (NA) content in the brain cortex decreased, while the NA level in the striatum and the 5-hydroxyindolacetic acid (5-HIAA) level in the brain cortex and the striatum as well as the MAO-T and MAO-A activities in the three brain structures increased. It is suggested that these and other changes observed in brain neurotransmission are an important element in the neurochemical bases of the age-related changes in behavior.

Aging↗