Effects of the nootropic agents adafenoxate, meclofenoxate and the acetylcholine precursor citicholine on the brain muscarinic receptors (experiments on rats).

The effect of adafenoxate (Af), meclofenoxate (Mf) and citicholine on the brain muscarinic receptors was studied in groups of ten male Wistar rats. The compounds were administered in doses of 50 mg/kg body weight twice daily for 7 days. One hour after the last treatment the animals were killed and the frontal cerebral cortex striatum, the hypothalamus and the hippocampus were removed immediately.

Changes in the 5-HT-binding sites in the cerebral cortex, striatum and hypothalamus of rats during ageing and under the effect of dopaminergic agents.

The changes in the 5-HT1-binding sites, developing during ageing and under the effect of 10-day administration of L-DOPA and haloperidol, were studied in the cerebral cortex, striatum and hypothalamus of 2-, 10- and 22-month-old rats. The values of Bmax of the 5-HT1-binding sites decreased in all three brain structures studied with the ageing of the experimental animals. Both L-DOPA and haloperidol did not change the general character of the changes in the number of 5-HT1-receptors, developing during ageing, but at the same time L-DOPA reduced their density in the three age periods and in the three cerebral areas studied, while haloperidol increased their number in the 2- and 10-month-old rats.

Age-related changes in brain biogenic monoamines and monoamine oxidase.

In experiments on 2-, 10- and 22-month old rats, it was found that essential age-related changes occurred in the brain level of biogenic monoamines (BMA) and in the monoamine oxidase (MAO) activity. In 22-month old rats the levels of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) markedly declined in most of the brain structures studied. 5-HT significantly decreased in the frontal cortex, striatum and hypothalamus.

A study of nootropic drugs for anti-anxiety action.

The effects of adafenoxate (100 mg/kg), aniracetam (50 mg/kg), meclofenoxate (100 mg/kg), piracetam (250 mg/kg), and standardized ginseng extract-G115 (100 mg/kg) applied for five days were studied with Vogel's conflict procedure in which thirsty naive rats were periodically administered shocks for licking water. The results showed a significant anti-anxiety effect (increases in licking) with adafenoxate and meclofenoxate. Piracetam significantly suppressed licking behaviour and this effect was evaluated as anxiogenic (resulting from the non-specific stimulant action of the drug).

Effects of structurally different (Leu5) enkephalinamides on electrically-evoked contractions of guinea pig ileum.

The incorporation of D-Leu5 and the substitution of L-Gly2 by D-Ala2 into (Leu5)enkephalinamide, using direct coupling of enzymatic and azide methods for peptide bond formation, increased the relative potency of (Leu5)enkephalinamides to inhibit the electrically-evoked contractions of guinea pig ileum, probably activating a delta-type opiate receptor.

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.

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.

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.

Bulgarian traditional medicine: a source of ideas for phytopharmacological investigations.

Some data about the use of medicinal plants in Bulgarian traditional medicine in the Middle Ages and in modern times are presented and the results of 40-year-long experimental-pharmacological investigations on many medicinal plants used in Bulgarian traditional medicine are reviewed. In-depth discussion is presented on the investigations of garlic (Allium sativum L.), a plant widely used by Bulgarian people for treating different diseases.

Effect of N-aminomethylpiperazine-3,3-diethyl-2,4-pyridinedione on the aggressive behaviour and avoidance training of rats with isolation syndrome.

The article investigates the effect of N-aminomethylpiperazine-3,3-diethyl-2,4-pyridinedione (DKMP), a newly-synthesized compound with a clearly manifested anticonvulsant action, on the aggressive behaviour and on the training for active two-way avoidance by using a shuttle-box. The effects of DKMP were compared with the effects of Diazepam on mouse killing behaviour and avoidance training both of isolated aggressive rats and of rats reared in groups. It was found that DKMP (100 mg/kg, subcutaneously) inhibited the aggressiveness in 88 per cent of the aggressive rats, whereas Diazepam (1 mg/kg, i.

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.

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.

The application of ethopharmacological techniques to behavioural teratology: preliminary investigations.

Ethopharmacological techniques were used to study the behaviour of the offspring of mice treated with different drugs before and after parturition. The "standard opponent" test was used and the animal's behaviour was recorded on videocassettes. It was found that ethyl alcohol, glutamate, cyproterone acetate, medroxyprogesterone acetate, corticosterone and thiourea changed, while lithium chloride and diazepam had no effect on social, defensive, threatening and aggressive behaviour.

Differences between the effects of two meclofenoxate doses on active training for two-way avoidance in rats.

Male Wistar rats were trained for active two-way avoidance in a shuttle-box apparatus for five consecutive days. Meclofenoxate, in doses of 100 and 300 mg/kg i.p.

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).

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.

Changes in brain opiate receptors in rats with isolation syndrome.

Prolonged social isolation of Wistar rats produces various neurochemical, neuroendocrine and behavioral changes. Some of isolated rats exhibit interspecies aggressive behavior (mouse-killing). It is suggested that social isolation leads to a stress-like state of rats.

[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.

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.

Pharmacological restoration of scopolamine-impaired memory.

In training for passive avoidance using a device of the step-down type, the nootropic agents piracetam (60 mg/kg orally) and centrophenoxine (100 mg/kg, i. p.) do not facilitate learning, while the ergot alkaloid elymoclavine (1 mg/kg, i.

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.

Effects of caffeine on aggressive behavior and avoidance learning of rats with isolation syndrome.

Caffeine at a dose of 40 mg/kg i.p. administered 60 min before testing for aggressive mouse-killing behavior in Wistar rats with isolation syndrome inhibited mouse-killing response in 48 per cent of the aggressive rats.

GABAergic influence on the effects of elymoclavine on exploratory behaviour of rats in open field.

The GABAergic influence on the effects of the ergot alkaloid elymoclavine on exploratory behaviour of rats in open field was studied using pharmacological tools. GABA was found to reduce the elymoclavine-stimulated exploratory behaviour. The GABAergic antagonists picrotoxin and bicuculline reversed the influence of GABA on the elymoclavine effects.