Effect of Surfagon on Open Field and Elevated Plus Maze Behavior of Gonadectomized and Non-Gonadectomized Male Rats.

We studied the effect of gonadotropin-releasing hormone agonist surfagon (2 µg/kg, once, intraperitoneally) on anxious behavior of adult gonadectomized and non-gonadectomized male rats. It was shown that surfagon significantly increased anxiety of both gonadectomized and non-gonadectomized rats in the open-field test and in elevated plus maze.

[Hypolipidemic activity of N-cholinergic antagonist Benzohexonium in the experiments ].

Methods: Experiments were carried out on outbred albino male rats (n = 150, 230-250 g). For modeling dislipoproteinemia (DLP) we used 3 models: single intraperitoneal injection of the detergent triton WR-1339; administration of ethanol; maintenance on a special hypercholesterolaemic diet (HD) during 21 days. Animals were divided into four groups: normal control, model group, gemfibrozil (Gfb) group, benzohexonium (Benz) group. Rats received per os benzohexonium (20mg/kg), reference drug gemfibrozil (50 mg/kg). We determined content of total cholesterol (TCh), triglycerides (TG) in samples of blood serum and liver, TCh in aorta. TCh, TG and Ch-HDL were analyzed spectrophotometrically using of standardized methods. Results: Compared with model group the contents of TCh, TG in serum and liver were significantly decreased in model + Benz group, whereas Ch-HDL was raised in rats fed special HD (P<0.05). Calculated index of atherogenity (TCh - Ch-HDL) / (Ch-HDL) showed the positive effect. Conclusion: The results obtained were shown the hypolipidemic activity of N-cholinergic antagonist Benzohexonium (20 mg/kg) lowered the content of lipids in blood, liver, and aorta.

Antiarrhythmic Activity of Taurepar during Ischemic and Reperfusion Damage to Myocardium.

The antiarrhythmic effect of taurepar, an N-phenylalkyl derivative of taurine, was examined in experiments on rats subjected to acute myocardial ischemia/reperfusion leading to arrhythmia development. During acute ischemia, taurepar (25 mg/kg) completely prevented early postocclusion arrhythmias including extrasystoles, ventricular tachycardia, and ventricular fibrillation. During postischemic reperfusion, taurepar (25 mg/kg) did not prevent extrasystoles and ventricular tachycardia, but precluded the development of ventricular fibrillation and the death of animals. The antiarrhythmic potency of taurepar surpassed that of lidocaine during acute myocardial ischemia and that of propranolol during ischemia/reperfusion injury. The results suggest that taurepar is a promising antiarrhythmic drug with high antifibrillation activity.

Antiarrhythmic effect of uridine and uridine-5'-monophosphate in acute myocardial ischemia.

Experiments on rats with acute myocardial ischemia accompanied by early postocclusive arrhythmias have shown normalizing, energy-stabilizing, and antiarrhythmic effects of uridine and uridine-5'-monophosphate. The drugs decreased lactate and restored reserves of glycogen and creatine phosphate depleted by ischemia. Uridine and uridine-5'-monophosphate significantly decreased the severity of ventricular arrhythmias. Both drugs reduced the incidence and duration of fibrillation. Uridine -5'-monophosphate demonstrated most pronounced antifibrillatory effectiveness. We hypothesize that the antiarrhythmic effect of the drugs is determined by their capacity to activate energy metabolism.

[Effect of galantamine and testosterone on the arthritic response and dopamine content in rat spleen].

The study was carried out on male Wistar rats with surgically ablated gonads. The rats with gonadectomy and intact rats received galantamine and/or testosterone over 10 days, after which the model arthritis was induced by injection of 200 ml of complete Freund's adjuvant. It was established that gonadectomy reduced arthritic reactions producing ulcer formation at a later time (21 days) as compared to control (rats with arthritis), where they are formed on the local stage of development (day 7). Testosterone replacement therapy completely blocks the development of ulcers on the paws. Galantamine suppresses the arthritic reaction more significantly, reducing paws and ankle-joint edema 1.5 and 1.3 times respectively (n = 12, p <0.05). The appearance of dopamine in the spleen during galantamine treatment may serve as a marker of protective action of the drug under hypoandrogenic conditions. Introduction of galantamine at high level of testosterone does not significantly influence on development of arthritic reaction, which is indicative of a marked imbalance between the hormonal and cholinergic systems and a possibility to modulate arthritic reaction with cholinergic drugs.

Effects of SCH-23390 and sulpiride on active avoidance in ovariectomized rats treated with a low dose of 17ß-estradiol.

We studied the effects of dopamine D1/D2 receptor antagonists on the dynamics of acquisition and extinction of active avoidance responses and open field behavior in ovariectomized female rats. Dopamine D1 receptor antagonist SCH-23390 (0.1 mg/kg intraperitoneally) and dopamine D2 receptor antagonist sulpiride (10.0 mg/kg intraperitoneally) were administered chronically (14 days) either alone or in combination with a low dose of 17ß-estradiol (0.5 µg per rat subcutaneously) to females after ovariectomy. It was found that SCH-23390 in combination with a low dose of 17ß-estradiol completely restored impaired conditioning and retention of a conditioned avoidance response in ovariectomized animals. Simultaneous correction of behavioral patterns in the open field test was also observed in ovariectomized females receiving SCH-23390. Sulpiride injected alone or in combination with low dose of 17ß-estradiol did not correct conditioning and reproduction of active avoidance response in females with estrogen deficiency and did not significantly affect animal behavior. The results indicate positive effect of dopamine D1 receptor blockade on active learning under conditions of estrogen deficiency.

[Chronic administration of RJR-2403 in combination with low-dose of 17beta-estradiol corrects passive avoidance learning in ovariectomized rats].

The aim of this work was to study the effect of stimulation or blockade of Na7-cholinoreceptors with a low dose of 17beta-estradiol on the passive avoidance performance and behavior in the open-field test in adult ovariectomized (OVX) female rats. Agonist of Na7-cholinoreceptors RJR-2403 (1.0 mg/kg, i.p.) or antagonist of Na7-cholinoreceptors mecamylamine (1.0 mg/kg, i.p.) treated chronically (14 days) alone and in a combination with low dose of 17beta-estradiol (0.5 microg/rat, s.c.) to OVX rats. Co-administration of RJR-2403 with low dose of 17P-estradiol completely restored impaired passive avoidance performance in OVX females. OVX rats treated with RJR-2403 and low dose of 17beta-estradiol demonstrated increased exploratory and grooming behavior in the open-field test. Both mecamylamine alone and in combination with low dose of 17beta-estradiol failed to influence the passive avoidance learning and failed to modify behavior in the open-field test in OVX rats. The results of the present study suggest positive effect of RJR-2403 in combination with low dose of 17beta-estradiol on passive avoidance learning at estrogen deficiency.

[Co-administration of NAN-190 with low dose of testosterone propionate improves passive avoidance performance in rats with androgen deficiency].

We have studied the effect of stimulation or blockade of the 5-HT(1A) receptors on the passive avoidance performance and open-field test behavior in gonadectomized (GDX) male rats of middle age treated with a low dose of testosterone propionate. of The 5-HT(1A) receptor agonist 8-OH-DPAT (0.05 mg/kg, s.c.) or 5-HT(1A) receptor antagonist NAN-190 (0.1 mg/kg, i.p.) were chronically (for 14 days) administered alone and in a combination with low dose of testosterone propionate (0.5 mg/kg, s.c.) in GDX rats of middle age (12 - 15 months). The co-administration of NAN-190 with low dose of testosterone propionate completely restored impaired passive avoidance performance in GDX males of middle age. Moreover, GDX rats of middle age treated with NAN-190 and low dose of testosterone propionate demonstrated increased exploratory and grooming behavior in the open-field test. Both 8-OH-DPAT alone and in combination with low dose of testosterone propionate markedly impaired passive avoidance learning and failed to modify behavior in the open-field test in GDX rats of middle age. The results of the present study are indicative of a positive effect of NAN-190 in combination with low dose of testosterone propionate on the passive avoidance learning at androgen deficiency in male rats of middle age.

Effect of uridine on energy metabolism, LPO, and antioxidant system in the myocardium under conditions of acute coronary insufficiency.

Experiments on rats have shown that preventive treatment with uridine stabilizes energy metabolism in the heart under conditions of 60-min left coronary artery occlusion. The preparation also prevented antioxidant system dysfunction and LPO hyperactivation. 5-Hydroxydecanoate, a selective blocker of mitochondrial ATP-dependent K(+)-channels, abolished the protective effect of uridine, which attested to the involvement of these channels into mechanisms of the cardioprotective effect of the preparation. The elimination of intravenously administered uridine from the blood of animals with acute ischemia was accelerated in comparison with that in intact animals, which could suggest the participation of this nucleoside in the processes of activation of intracellular anti-ischemic defense mechanisms.

A new activity of N-cholinolytic drug benzohexonium.

We have found that N-cholinolytic drug benzohexonium produces a hypolipidemic effect: it reduces dyslipoproteinemia, fatty infiltration of the liver, and risk of atherosclerotic lesions.

Development of laboratory rats receiving silver-enriched ration for a long time.

We studied the effect of silver ions on the status and metabolism of copper in rats receiving Ag-diet from the first day of life and for 6 months. The effect of silver ions on copper metabolism was assessed by body weight, relative weight of organs (body weight/organ weight), oxidase activity, content of immunoreactive ceruloplasmin and copper concentration in blood serum, by the expression of copper-transporting protein genes in the liver, and copper and silver distribution in liver and brain cells. Brain functions were evaluated by open-field behavior and passive avoidance conditioning. No acute deficiency of ceruloplasmin-associated copper was observed in rats receiving silver-enriched diet starting from the early postnatal period; copper metabolism in the liver did not change, psychoemotional state and memory corresponded to the control. However, Ag-diet almost 2-fold decelerated the growth of experimental rats. We hypothesize the existence of an unknown mechanism of copper delivery to organs in rats that is activated during the early ontogeny under conditions of ceruloplasmin-associated copper deficiency.

[Effects of new amino acid derivates of dopamine on anxiety-like behavior].

This study was aimed at a comparative analysis of the effects of new amino acid derivatives of dopamine (IEM-2111, IEM-21122, IEM-2123, IEM-2126) on anxiety-like behavior in rats. The behavioral effects of the dopamine-like substances were evaluated under conditions of acute and chronic experiments. In acute experiment, a single dose of substances was administered 45 min prior to the behavioral testing of animals. In chronic experiment, the synthesized compounds were administered in a single daily dose for 14 days. Pharmacological analysis of the effect of drugs was performed in the following doses: 0.1, 1.0, and 10.0 mg/kg (i.p., introduction). Diazepam was used as a reference drug that was introduced in a dose of 1.0 mg/kg (i.p.). The anxiety-like state was determined using the elevated plus maze test, while the behavioral effects were evaluated in the open field test. It was found that IEM-2111, IEM-2122, and IEM-2123 exhibited anxiolytic action under condition of chronic administration, whereas IEM-2126 produced an anxiolytic effect only after acute administration. The introduction of left optical isomers of aromatic or heterocyclic radicals of amino acids into the molecule of 3,4-dimetoxyphenylethylamine results in a more pronounced anxiolytic effect upot chronic administration. The degree of action of the new amino acid derivatives of dopamine has a dose-dependent character, and the maximum effect is manifested at a dose of 1.0 mg/kg.

[Stimulation of D1-receptors improves passive avoidance learning of female rats during ovary cycle].

The involvement of D1-receptors in learning/memory processes during ovary cycle was assessed in the adult female rats. SKF-38393 (0,1 mg/kg, i.p.), D1-receptor agonist and SCH-23390 (0,1 mg/kg, i.p.), D1-receptor antagonist were injected chronically to adult female rats. Learning of these animals was assessed in different models: passive avoidance performance and Morris water maze. Chronic SKF-3839 administration to females resulted in the appearance of the passive avoidance performance in proestrous and estrous, as distinct from the control animals, but failed to change the dynamics of spatial learning in Morris water maze. Chronic SCH-23390 administration similarly impaired non-spatial and spatial learning in females during all phases of ovary cycle. The results of the study suggest modulating role of D1-receptors in learning/memory processes during ovary cycle in the adult female rats.

[Hypolipidemic activity of trimethylglycine].

Hypolipidemic properties of a native trimethyl derivative of glycine, trimethylglycine (TMGl), were studied in hyperlipidemic rats and guinea pigs. The administration of TMGl to the hyperlipidemic rats and guinea pigs produced a pronounced hypolipidemic effect. A positive action of TMGl on the lipid profile of blood serum of the experimental animals was observed as manifested by a decrease in the level of cholesterol of low density lipoproteins (LDL) and an increase in the cholesterol level of high density lipoproteins (HDL).

[Administration of quinpirole with 17beta-estradiol in low doses corrects active avoidance performance in ovariectomized female rats].

The influence of D1/D2 types of dopaminergic receptors on the dynamics of acquisition and extinction of active avoidance performance and the behavior of ovariectomized female rats has been studied in the open field test. The DI-type dopaminergic receptor agonist SKF-38393 (0.1 mg/kg, i.p.) and D2-type dopaminergic receptor agonist quinperole (0.1 mg/kg, i.p.) were administered chronically (14 days) alone or in combination with low dose of 17beta-estradiol (0.5 microg/rat, s.c.) in animals after ovariectomy. It is established that quinperole in combination with low dose of 17beta-estradiol completely corrected impairments in the mechanisms of formation and retention of active avoidance performance in ovariectomized females. After quinperole treatment, this effect was also accompanied by the correction of behavior in the open field test. In contrast, the administration of SKF-38393 alone or in combination with low dose of 17beta-estradiol in female rats with estrogen deficiency neither corrected the formation and reproduction of active avoidance response of animals nor modified their behavior in the open field test. The results of the present study suggest important role of D2-type dopaminergic receptors in active avoidance performance development in animals with estrogen deficiency.

Pharmacological correction of testosterone deficiency during experimental myocardial ischemia.

Experiments on rats with myocardial ischemia modeled by occlusion of the left coronary artery aggravated by alimentary dislipoproteinemia showed that therapy with taurepar (50 mg/kg), a taurine derivative, decreased blood corticosterone concentration and increased the level of endogenous testosterone, which attests to normalization of the compensatory-adaptive and gonadotropic functions of the organism.

Effects of cholinergic agonists and antagonists under conditions of spleen denervation in rats with endotoxic shock.

Model experiments on rats with endotoxic shock induced by intraperitoneal injection of LPS Salmonella Typhi strain ty-4441 (20 mg/kg) showed that crossing of the vagus nerve innervating the spleen increased HR, stimulated production of antibodies, and moderated serotonergic activity of splenocytes. Pharmacological correction of the shock with muscarinic receptor antagonist atropine and its combinations with anticholinesterase agent galantamine or muscarinic and nicotinic cholinoreceptor agonist choline alfoscerate 30 min before shock modeling moderated HR and normalized B cell functions and serotonin level in the spleen.

[The effect of taurine derivative of change the biochemical parameters carbohidrate and lipide status by starvation].

The results obtained on the model of starvation shows that nutritional dropsy led to the significant decrease of glucose, total cholesterol (TCh) and triglycerides (TC), as well as increase of non-estherified fatty acids (NEFA) in blood serum. In the rats with nutritional dropsy after treatment fed with standard diet enriched with soybean protein body weight returned to normal values as well as levels of Glucose, TCh and TC. However, concentration of NEFA remained increased. In the experimental group received additionally taurepar or taurhythman the level of NEFA decreased up to the normal one. It is necessary to mention that taurine derivatives did not change the biochemical parameters in blood of normal non-starved rats. We suppose that these new substances promote reduction of intensity of hyperlipidemic processes. It is known, that during starvation incomplete oxidation of fatty acids leads to acidosis with following destruction of mitochondria membraine. Finding property of taurine derivatives to decrease the concentration of non-estherified fatty acids points at their ability for restoration of tricarboxilic acid's cycle and prevention of accumulation of suboxidized molecules of NEFA and acidosis development.

[Anti-inflammatory role of cholinergic and serotonergic systems in shock].

Development of anaphylactic shock initiated with the horse serum (anaphylactic index = 4.0 +/- 0.0 arbitrary units) leads to acute decrease in spleen concentration of serotonin (in shock--0.443 +/- 0.005; basal level--1.532 +/- 0.004 ng per mg of protein). Unlike of anaphylaxis, development of endotoxic shock in rats, caused by introduction of a sublethal dose (20 mg/kg) of lipopolysaccharide, results in acute increase in serotonin concentration (at a shock--56.588 +/- 0.006, basal level--5.465 +/- 0.005 ng per mg of protein) and marked tachycardia (+76 +/- 8, intact rats--+2 +/- 1 beats per min). Administration of atropine with galantamine leads to the most essential decrease of anaphylactic reaction (1.5 +/- 0.3 arbitrary units). Administration of choline alfoscerate (-16 +/- 3 beats per min) or galantamine (+9 +/- 2 beats per min) significantly reduces tachycardia. Data show, that inhibition of the central cholinergic mechanisms leads to increase and their excitation--to decrease in activity of the spleen serotonergic system. So, spleen concentration of serotonin is connected with a target of shock defeat (lungs or heart).