Effect of Chronic Administration of Obestatin and Its Fragment FNAP-NH2 on Behavioral Activity and Nociceptive Threshold in Rats with Normal and Excess Body Weight.

The effects of chronic intranasal administration of 300 nmol/kg obestatin and its fragment FNAP-NH2 on behavioral activity and nociceptive threshold were examined in male Wistar rats with normal body weight or alimentary obesity. In normal rats, obestatin produced no effect on behavior and nociception, whereas FNAP-NH2 fragment enhanced risk-taking behavior. Rats with excess body weight demonstrated less pronounced risk-taking behavior and elevated nociceptive threshold in comparison with normal animals, but these differences were abolished by chronic administration of FNAP-NH2.

Changes in Behavior and Blood Corticosterone Level in Male and Female Rats after Single Administration of Obestatin Fragment 1-4.

Single administration of the obestatin fragment 1-4 (300 nmol/kg) to male Wistar rats produced a significant weight loss in male rats on observation days 5-8, while in female rats only on day 8. In addition, males demonstrated decreased risk factor in the elevated plus-maze test, but no effect of the preparation on behavior of female rats was revealed. Obestatin fragment 1-4 had no effect on corticosterone level 1 week after single administration in both females and male rats.

Antioxidant Defense System after Single and Chronic Administration of Obestatin and Its Fragment (1-4) to Normal and Overweight Male Rats.

We studied the effects of anorectic peptide obestatin and its fragment (1-4) on the antioxidant defense system in animals with normal and experimentally induced increased body weight. In rats with normal body weight, no changes in activity of the antioxidant defense system 1 week after single administration of the substances. After chronic administration of obestatin and fragment (1-4) for 1 week, total antioxidant capacity of the plasma decreased; obestatin also lowered the content of TBA-reactive products. In the overweight rats, SOD-like activity in the plasma increased 1 week after chronic administration of obestatin. Hence, obestatin and its fragment (1-4) induced changes in the antioxidant defense system only after chronic administration.

[Effects of neonatal fluvoxamine administration to white rats and their correction by semax treatment].

The aim of this work was to study the delayed effects of chronic neonatal administration of the selective serotonin reuptake inhibitor fluvoxamine (FA) to white rat pups and to estimate the possibility to correct these effects by treatment with semax. Fluvoxamine was injected intraperitoneally at a dose of 10 mg/kg from postnatal days 1 to 14, and semax was injected intranasally at a dose of 0.05 mg/kg from postnatal days 15 to 28. It was shown that neonatal FA administration produced a significant delay in animal somatic growth. A loss in body weight was detected both during FA administration and 4-6 weeks after the last injection. Furthermore, FA administration increased the anxiety level and disturbed the learning ability of animals. The negative consequences of neonatal FA administration were largely compensated by Semax.

Effect of anorexigenic peptide obestatin on platelet aggregation and osmotic resistance of erythrocytes.

We studied the effects of the anorexigenic peptide obestatin on the coagulation system and blood rheology (by the parameters of platelet aggregation and osmotic resistance of erythrocytes) in vitro and in vivo. Obestatin inhibited in vitro platelet aggregation in the entire dose range and reduced osmotic resistance of erythrocytes in all doses except 300 nmol/kg (obestatin in a dose of 300 nmol/kg had no effect on this parameter). Similar to the results of in vitro experiments, intranasal, intraperitoneal, and subcutaneous administration of obestatin in a dose of 300 nmol/kg inhibited platelet aggregation and had no effect on the osmotic resistance of erythrocytes.

Optimization of choline administration regimen for correction of cognitive functions in rats after brain injury.

Choline diet promotes improvement of the brain cognitive functions in rats with moderate-to-severe traumatic brain injury. In previous studies, the rats received choline being standard (0.2%) or choline-supplemented (2%) diet for 2 weeks prior to and 2 weeks after experimental brain injury. To the end of the experiments (in 4 weeks), the post-traumatic disturbances in the cognitive functions were observed in both groups, although they were less pronounced than in the rats kept on the choline-supplemented diet. Based on original mathematical model, this paper proposes a method to calculate the most efficient use of choline to correct the brain cognitive functions. In addition to evaluating the cognitive functions, the study assessed expression of α7 nicotinic acetylcholine receptors, the amount of consumed food and water, and the dynamics of body weight.

[Opposite Semax influence on conditioning and functional disturbances of avoidance responses in rats].

Semax effects on formation of active avoidance reaction in rats in different experimental models have been studied. It was shown that intraperitoneal Semax administration at a dose of 0.05 mg/kg accelerated acquisition of one-way active avoidance response when rats were trained to avoid electric foot-shock by jumping on the shelf. When rats were trained in shuttle-box the peptide increased the electroshock threshold value required to provocation of rat moving in experimental box and delayed acquisition of two-way active avoidance response. At the same time Semax stimulated avoidance response restoration in shuttle-box after functional disturbances induced by acute modification of cause-effect and spatial relationships in experimental environment. Data obtained support nootropic properties of Semax.

[Selective D1-receptor antagonist SCH23390 decreases maternal reactions in rats upon acute and chronic injections in postpartum period].

The influence of the D1-receptor antagonist SCH23390 on the maternal behavior of female rats has been studied. It is established that a comparatively high dose of the drug (acute injections) significantly decreases both the locomotor activity and manifestations of the parental care. Lower dosages do not affect the locomotor activity, but still suppress the maternal behavior (after both acute and chronic injections of SCH23390). The obtained results are discussed in terms of the analysis of the maternal motivation mechanisms and the development of the D1-induced postpartum depression.

[The role of dopamine and opioid systems in the regulation of maternal behavior].

This review describes in detail the different components and neuroanatomical basis of maternal behavior and also methodological approaches to investigation of parental reactions. The contributions of some endocrinal and neuromediator brain systems (in the first place, opioid and dopaminergic) to the regulation of maternal behavior are reported. The influences of ligands of opioid and dopamine receptors on the expressions of paternal reactions are analyzed especially. In concluding part the reasons of maternal depression and possibilities of this malfunction pharmacological correstion are discussed.

[A new method of investigation of "child's" behavior (infant-mother attachment) of newborn rats].

A new method of studying "child's" (maternal bonding) behavior of newborn rats was developed. The efficiency of the method was proved in estimation of dopaminergic control of the infant-mother attachment. Selective D2-antagonist clebopride applied in subthreshold for motor activity doses caused a decrease in aspiration of pups to be in contact with a dam. On the basis of features analyzed (latent periods and expression of various behavioral components), the integrated criterion for the estimation of "child's" reactions was suggested. Application of this criterion made it possible to neutralize high individual variability of the behavior typical of newborns.

[Influence of Semax on the emotional state of white rats in the norm and against the background of cholecystokinin-tetrapeptide action].

The effects of the adrenocorticotropic hormone (ACTH(4-10)) analog, Semax (MEHFPGP), on the level of anxiety and depression in white rats have been studied in the normal state and against the background of cholecystokinin-tetrapeptide (CCK-4) action. Semax was injected intranasally in doses of 50 and 500 microg/kg 15 min before the testing. CCK-4 was administered intraperitoneally in a dose of 400 microg/kg 40 min before the testing. The level of anxiety was estimated in the elevated plus-maze test, and the degree of depression, in the forced swimming test. Semax administration did not influence the emotional state of animals in the normal state. The CCK-4 injection led to an increase in anxiety and depression in rats. Semax normalized the animal behavior disturbed by the CCK-4 administration, which attests to its anxiolytic and antidepressant effects at elevated levels of anxiety and depression.

[Nootropic and analgesic effects of Semax following different routes of administration].

Heptapeptide Semax (MEHFPGP) is the fragment of ACTH(4-10) analogue with prolonged neurotropic activity. The aim of the present work was to study the Semax effects on learning capability and pain sensitivity in white rats following intraperitoneal and intranasal administration in different doses. Semax nootropic effects were studied in the test of acquisition of passive avoidance task. Pain sensitivity was estimated in Randall-Selitto paw-withdrawal test. It was shown that Semax exerts nootropic and analgesic activities following intraperitoneal administration. Analysis of dependence of these effects on dose resulted in different dose-response curves. Following intranasal administration, Semax was more potent in learning improvement compared to intraperitoneal administration. The peptide failed to affect the animal pain sensitivity following intranasal administration as opposed to intraperitoneal administration. The data obtained suggest different mechanisms and brain structures involved in realization of the nootropic and analgesic effects of Semax.

[Study of long-lasting effects of acute prenatal stress induced forced swimming].

The aim of the present work was to assess long-lasting effects of acute prenatal stress in white rats. Forced swimming in cold water on the 7th or the 14th gestational day was used as a prenatal stressor. The prenatal stress led to low birthweight of offspring and their delayed growth rate during the second month of life. Prenatally stressed animals showed abnormalities in exploratory behavior and anxiety, increased emotionality and impaired learning capabilities at the age of 1-2 month. Consequently, acute stress on the 7th and at the 14th day of pregnancy induced long-lasting negative behavioral changes in offspring of stressed white rats.

[Melanocortin system].

Melanocortin system consists of native melanocortin peptides (ACTH, MSH and their fragments), melanocortin receptors (MC1R-MC5R) and their endogenous antagonists. Melanocortins have a wide spectrum of physiological activity. These peptides improve memory and attention, facilitate neuromuscular regeneration, exert neuroprotective action, affect the development of nervous system, modulate sexual behavior, have anti-inflammatory and antipyretic effects, interact with opioid system, affect the pain sensitivity and cardiovascular system, decrease food intake and body weight, influence on exocrine secretions.

[Delayed effect of exorphins on learning of albino rat pups].

The delayed effect of food-derived opioid peptides (exorphins) after chronic administration on postnatal days 1-14 on the learning of albino rat pups has been studied. Heptapeptide YPFPGPI (beta-casomorphin-7), pentapeptide YPLDL (rubiscolin-5) and pentapeptide YPISL (exorphin C) improved the development of the conditioned foraging reflex in a complex maze. Hexapeptide PFPGPI lacking the N-terminal tyrosine proved inefficient. Only beta-casomorphin-7 had an effect (negative) on passive avoidance conditioning. The obtained data confirm that exorphins (particularly, milk-derived beta-casomorphins) can have significant and long-term effects on the environmental adaptation of young mammals.

[Studying the nootropic effects of betamecil].

Comparative study of the effects of methyluracil and betamecil showed that a fourfold oral administration of betamecil in a dose of 10 mg/kg leads to a considerable increase in the orientation-and-search reaction in the open field test. This drug effect is retained for at least one week. Betamecil in doses of 10 and 100 mg/kg does not virtually alter the rate of conditioning of the food-seeking reflex with respect to the place in the T-shaped maze test (as compared to the control animals. However, certain acceleration of the learning process is observed as compared to the animals treated with methyluracil. The chronic administration of betamecil (for 18 days) results in improved preservation and reproduction of the previously conditioned food-seeking habit. Neither piracetam nor methyluracil produced such effects. The results suggest that betamecil in indicated doses exhibits a nootropic activity.