Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress.

Current antidepressant therapy shows substantial limitations, and there is an urgent need for the development of new treatment strategies for depression. Stressful events and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis play an important role in the pathogenesis of depression. HPA axis activity is self-regulated by negative feedback at several levels including adrenocorticotropic hormone (ACTH)-mediated feedback.

The Effect of the Agonist Cholecystokinin-4 D-GB-115 On the Character of Motor Activity of Paramecium caudatum.

The study investigated the effect of GABA in various concentrations and D-GB-115 at a concentration of 10 M on the behavior of Paramecium caudatum. It was shown that GABA increases motor activity and changes the movement strategy of these protozoans, and the dose-effect relationship is domed, which can be explained by the presence of two types of GABA receptors in the outer membrane of paramecia: GABA-A and GABA-B. The active concentrations of GABA range from 10 to 10 M.

A Low-Molecular-Weight BDNF Mimetic, Dipeptide GSB-214, Prevents Memory Impairment in Rat Models of Alzheimer's Disease.

Brain-derived neurotrophic factor (BDNF) is known to be involved in the pathogenesis of Alzheimer's disease (AD). However, the pharmacological use of full-length neurotrophin is limited, because of its macromolecular protein nature. A dimeric dipeptide mimetic of the BDNF loop 1, bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylene diamide (GSB-214), was designed at the Zakusov Research Institute of Pharmacology.

Method for Primary Screening of Pharmaceuticals on the Paramecium caudatum Eukaryotic Cell Model.

The  effect  of  adrenaline  in  various  concentrations  and  dopamine  at  a  concentration  of 10 mol/mL on the behavior of Paramecium caudatum was studied. It is shown that adrenaline reduces motor activity and changes the movement strategy of these protozoans; a dose-dependent behavioral response on the drug concentration was observed. This effect can be explained by the presence of adrenaline receptors located on the surface of the cell membrane.

The snake heart pacemaker is localized near the sinoatrial valve.

To provide the first description of the exact location of primary pacemaker of the squamate heart, we used sharp microelectrode impalements and optical mapping of isolated sinus venosus preparations from Burmese pythons. We located the dominant pacemaker site at the base of the right leaflet of the sinoatrial valve (SAV), but latent pacemakers were also identified in a circular region around the SAV. Acetylcholine (10-5 mol l-1) or noradrenaline (10-6 mol l-1) induced shifts of the leading pacemaker site to other points near the SAV.

Semax prevents learning and memory inhibition by heavy metals.

Separate and joint effect of Semax, ascorbic acid, lead diacetate, and ammonium molybdate on avoidance conditioning in rats was studied. It was established that the heavy metal salts inhibited the avoidance response, and the peptide counteracted this inhibition as strongly as ascorbic acid or to a comparable degree. These findings confirm the antioxidant properties of Semax.

[Food-derived opioid peptides and their neurological impact].

In this review the up-to-date literature data about exorphins are analysed. Exorphins are short opioid-like food-derived peptides. Different reports about their physiological impact in animals and humans are reviewed with focus on neurotropic effects.

Increasing the Efficiency of Parkinson's Disease Treatment Using a poly(lactic-co-glycolic acid) (PLGA) Based L-DOPA Delivery System.

To compare the efficacy of L-DOPA administered intranasally in the form of nanoparticles (nano-DOPA) and in standard drug forms using a rat Parkinson's Disease (PD) model. L-DOPA-containing nanoparticles (250±50 nm) were synthesized using the double emulsion method. The efficacy of nano-DOPA therapy was studied in Wistar rats with 6-OHDA-induced PD.

Effect of single and repeated injections of selective D2-antagonist clebopride on maternal behavior of albino rats.

This study examined the effect of clebopride at low concentration that did not modify the motor activity on the parental care in female albino rats. Single injection of the drug attenuated the parental care reactions on postinjection minute 20, but not one day thereafter. The daily injection of the drug during the post partum period (1-6 days) resulted in significantly more pronounced and stable effects.

Behavioral effects of original tetrapeptide, an analog of N-terminal nociceptin fragment.

The study examined the effect of an analog to N-terminal nociceptin fragment AcOH×Phe-Gly-Gly-Phe-NH(2) on the behavior of albino rats. This tetrapeptide (5 μg/kg intraperitoneally) significantly enhanced motor and exploratory activity in mature rats and in 42-day pups and produced opposite effects in 21-day rat pups, which attests to the complex dynamics of maturation of nervous structures involved in the realization of nociceptin action.

Blood-brain barrier unlocked.

The brain is protected by a physiological blood-brain barrier (BBB) against toxins and some metabolites circulating in the blood. At the same time, the BBB limits penetration into the brain of many neuroactive drugs. Efficient ways to increase BBB permeability for delivery of drugs of different chemical nature into the brain are unknown.

Semax attenuates the influence of neonatal maternal deprivation on the behavior of adolescent white rats.

Maternal deprivation in the early postnatal period significantly affects the behavior and development of different animals. Here we studied delayed effects of daily maternal deprivation (5 h/day) on physical development and behavior of white rats during postnatal days 1 to 14. Here we studied the possibility of reducing the negative consequences of deprivation by daily intranasal treatment with Semax, an analog of ACTH(4-10), in a dose of 0.

Correction of long-lasting negative effects of neonatal isolation in white rats using semax.

Adverse experience during the early postnatal period induces negative alterations in physiological and neurobiological functions, resulting in long-term disorder in animal behavior. The aim of the present work was to study the long-lasting effects of chronic neonatal stress in white rats and to estimate the possibility of their correction using Semax, an analogue of ACTH fragment (4-10). Early neonatal isolation was used as a model of early-life stress.

Role of the brain dopaminergic and opioid system in the regulation of "child's" (maternal bonding) behavior of newborn albino rats.

Administration of D(2) receptor antagonist clebopride in a dose not affecting locomotor activity was followed by a decrease in maternal bonding behavior of 10-day-old and 15-day-old albino rat pups. D(1) receptor antagonist SCH23390 had a stimulatory effect only on the behavior of 10-day-old newborns. Opioid peptide β-casomorphin-7 abolished the effect of clebopride in rat pups of the older age group.

Delayed nootropic effects of arginine vasopressin after early postnatal chronic administration to albino rat pups.

Intranasal administration of arginine vasopressin (10 microg/kg) to albino rat pups had a strong nootropic effect during training with positive and negative reinforcement. This effect was different in animals of various age groups: training with positive reinforcement was improved in "adolescent" rats and pubertal animals, while during training with negative reinforcement, the nootropic effect of the peptide was more prolonged and persisted also in adult animals.

Behavioural effects in mice and intoxication symptomatology of weak neurotoxin from cobra Naja kaouthia.

Weak neurotoxins belong to the superfamily of three-finger toxins from snake venoms. In general, weak toxins have a low toxicity and, contrary to other three-finger toxins, their molecular targets are not well characterized: in vitro tests indicate that these may be nicotinic acetylcholine receptors. Here, we report the influence of intraperitoneal and intravenous injections of weak neurotoxin from Naja kaouthia venom on mouse behaviour.

Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain.

The heptapeptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is an analogue of the N-terminal fragment (4-10) of adrenocorticotropic hormone which, after intranasal application, has profound effects on learning and memory formation in rodents and humans, and also exerts marked neuroprotective effects. A clue to the molecular mechanism underlying this neurotropic action was recently given by the observation that Semax stimulates the synthesis of brain-derived neurotrophic factor (BDNF), a potent modulator of synaptic plasticity, in astrocytes cultured from rat basal forebrain. In the present study, we investigated whether Semax affects BDNF levels in rat basal forebrain upon intranasal application of the peptide.

Enhanced activity of DNA polymerase iota in mouse brain cells is associated with aggressiveness.

Recent studies performed with crude extracts of mouse tissues showed that the activity of DNA-polymerase iota (Pol iota) can be detected only in brain and testis extracts. To assess whether the activity of Pol iota is associated with animal behavior, we determined Pol iota activity in brain extracts of mice of two lines sharply differing in aggressiveness (RSB and RLB). We found that Pol iota activity in the mice with aggressive behavior was three times higher than in the less aggressive mice.

In vitro and in vivo opioid activity of [DPro(6)]dermorphin, a new dermorphin analogue.

To study the effects of inducing stereo-chemical modifications in the structure of dermorphin (DM) so as to improve its mu-opioid receptor affinity and its resistance to C-terminal enzymatic degradation, in the Institute of Molecular Genetics of Moscow, we synthesized a new DM analogue ([DPro(6)]DM) and analyzed the changes induced in the biological activities of DM by substituting the Pro(6) residue with DPro(6). We compared the activity of the new DM analogue and DM in in vitro assays and in in vivo tests of analgesia, thermoregulation, heart rate recordings, and gastrointestinal motility in rats. In the in vitro tests, guinea pig ileum (GPI) and mouse vas deferens (MVD), although the opioid activities of [DPro(6)]DM indicated that the peptide was always less potent than DM, its lower IC(50) ratios (mu/delta) showed that it had higher mu-opioid receptor selectivity.