Effects of afobazole on cognitive behavior of the offspring of rats exposed to tobacco smoke during gestation period.

Experiments on the model of foraging behavior formation under conditions of free choice (T-maze) revealed learning failure against the background of reduced motor activity in the offspring of rats exposed to tobacco smoke on gestation days 1-20. Afobazole administered to pregnant rats orally in doses of 1 or 10 mg/kg daily during the whole gestation and/or entering rat pup body with breast milk from mothers receiving 200 mg/kg to day 20 of their life normalized their learning capacity. The formation of short-term and long-term memory in animals receiving afobazole did not differ from the control. Hence, afobazole corrects cognitive disorders in rats exposed to tobacco smoke during prenatal development.

[The original nootropic and neuroprotective drug noopept potentiates the anticonvulsant activity of valproate in mice].

The influence of the original dipeptide drug noopept, known to possess nootrope, neuroprotector, and anxiolytic properties, on the anticonvulsant activity of the antiepileptic drug valproate has been studied on the model of corazole-induced convulsions in mice. Neither a single administration of noopept (0.5 mg/kg, i.p.) nor its repeated introduction in 10 or 35 days enhanced the convulsant effect of corazole, which is evidence that noopept alone does not possess anticonvulsant properties. Prolonged (five weeks) preliminary administration of noopept enhanced the anticonvulsant activity of valproate. This result justifies the joint chronic administration of noopept in combination with valproate in order to potentiate the anticonvulsant effect of the latter drug. In addition, the administration of noopept favorably influences the cognitive functions and suppresses the development of neurodegenerative processes.

Early postnatal effects of noopept and piracetam on declarative and procedural memory of adult male and female rats.

We studied the effect of a new nootropic dipeptide Noopept and reference nootropic preparation piracetam injected subcutaneously on days 8-20 of life on learning of alternative feeding response in a 6-arm-maze in male and female rats. Early postnatal administration of Noopept disturbed the dynamics of learning by parameters of declarative and procedural memory. Piracetam impaired learning by parameters of procedural, but not declarative memory (only in males). Both preparations decreased the ratio of successfully learned males (but not females). The observed effects were not associated with changes in locomotor activity.

[Comparative study of the long-term behavioral effects of noopept and piracetam in adult male rats and female rats in postnatal period].

Adult male and female rats were treated with the peptide nootrope drug noopept (daily dose, 0.1 mg/kg) and piracetam (200 mg/kg). In the period from 8th to 20th day, both drugs (cognitive enhancers) suppressed the horizontal and vertical activity and the anxiety in test animals as compared to the control group treated with 0.9 % aqueous NaCl solution. Early postnatal injections of the nootropes influenced neither the morphology development nor the behavior of adult female rats in the plus maze, extrapolational escape, passive avoidance, and pain sensitivity threshold tests. Animals in the "intact" group (having received neither drugs not physiological solution, that is, developing in a poor sensor environment), showed less pronounced habituation in the open field test as compared to the control and drug treated groups.

[Antiamnesic activity of nerve growth factor adsorbed on poly(butyl) cyanoacrylate nanoparticles coated with polysorbate-80].

The antiamnesic activity of nerve growth factor (NGF) in various medicinal forms [aqueous NGF solution with and without polysorbate-80 (PS-80) additives, NGF adsorbed on poly(butyl) cyanoacrylate (PBCA) nanoparticles with and without PS-80 coating] has been studied in rats with model amnesia induced by scopolamine (2 mg/kg, s.c.). The antiamnesic activity was evaluated by the ability of subsequently introduced drugs (5 microg NGF per animal, i.p.) to inhibit the amnesic action of scopolamine as manifested by retrieval of the passive avoidance reflex (PAR) learned using the Lafayette Instruments USP system 30 min after drug injection. The PAR memory trace was evaluated as an increase in the latent time before visiting the dark compartment 24 h after drug injection. In the untreated amnesia control group, the scopolamine amnesia was manifested by the absence of any increase in the PAR latent time. In the form of an aqueous solution, NGF did not inhibit the scopolamine-induced amnesia. NGF adsorbed on uncoated PBCA and in the form of solution with PS-80 produced an antiamnesic action manifested by a reliable increase in the PAR latent time as compared to that in the untreated control group. NGF adsorbed on PBCA nanoparticles coated with PS-80 not only exhibited a significant antiamnesic effect, but even stimulated the cognitive function and increased the PAR latent time above the value in the learned control group.

[Experimental and clinical rationale for complex treatment of mental disorders in clean-up workers of the Chernobyl nuclear plant accident]. / Eksperimental'noe i klinicheskoe obosnovanie kompleksnogo primeneniia piratsetama i gidazepama pri lechenii psikhicheskikh rasstroistv u likvidatorov katastrofy na Chernobyl'skoi AES.

Piracetam is an effective drug for the treatment of asthenic and intellectual-mnestic disorders. However, this drug induces superfluous stimulation which reduces the therapeutic effect in rescuers after Chernobyl nuclear power disaster. The results of experimental and clinical investigations show that the administration of gidazepam--an atypical benzodiazepine tranquilizer--in combination with piracetam produces correction of the undesired stimulant action of the latter drug, while potentiating the nootropic (antiamnesic) and anxiolytic effects. This drug interaction led to an improvement in the therapy.

[The effect of training conditions on passive avoidance performance in rats]. / Zavisimost' vosproizvodimosti uslovnogo refleksa passivnogo izbeganiia ot uslovii ego vyrabotki u krys.

Male outbred rats were trained for step-through avoidance in different experimental conditions: 1) in a two-compartment chamber with a small dark compartment and a chamber with illuminated suspended platform; 2) with or without acquaintance with experimental chamber 24 hours prior to learning; 3) with or without a possibility of the chamber exploration 3 min immediately before training procedure; 4) with inescapable or escapable pain reinforcement (5 electric footshocks, 0.45 mA, 1 s, with 2-s between-shock intervals); 5) with 2 or 5 inescapable footshocks of the same rate, duration, and intensity. The acquired performance was tested 24 h after training. It was shown that the procedure of exploration of the experimental chamber 24 prior to training improved the reproduction and the same procedure conducted immediately before training impaired the reproduction of the acquired behavior. Different training conditions improved the reproduction of the acquired behavior in the chamber with a suspended platform to a greater extent than in the two-compartment chamber. The decrease in the number of pain stimuli from 5 to 2 or the possibility to escape the punishment during training did not significantly change the reproduction.

[Is "scopolamine-induced amnesia" in rats the result of state-dependent learning?]. / Iavliaetsia li "skopolaminovaia amneziia" u krys rezul'tatom oblucheniia, zavisiiashchego ot sostoianiia?

The effects of a single and repetitive administration of m-cholinoblocker scopolamine (Sc) to male rats on retention of step-through passive avoidance (PA) or active avoidance (AA) in a shuttle-box were compared. In case of PA Sc (1 mg/kg) was injected i.p. only 30 min before training, only 30 min before testing, or both before training and before testing. In case of AA Sc (0.5 mg/kg/day) was injected i.p. only 15 min before each training session or both before training and before testing (44 days after achievement of learning criterion). The PA and AA retention were impaired only in the experiments, where the drug was administered before training, but did not differ from control, when Sc was injected twice. The Sc-induced amnesia (like many other cases of memory deficits) is suggested to be a manifestation of state-dependent learning. Similarity between the brain state during memory consolidation and during the retention test is necessary for recollection.

[The effect of the new nootropic dipeptide GVS-111 in different functional disorders of the escape reaction]. / Effekt novogo nootropnogo dipeptida GVS-111 pri razlichnykh funktsional'nykh narusheniiakh reaktsii izbeganiia.

The authors studied the effect of a new nootropic agent with anxiolytic properties GVS-111 (ethyl ether N-phenylacetyl-L-prolylglycine) on formation of the avoidance reaction (AR) in rats and its functional disorders which were induced by two methods. In one case the stereotype of the relations between the stimulus, reaction and its consequence which developed during the experiment were urgently disturbed: the change of the animal to the other half of the chamber in response to a conditioned stimulus did not lead to its cutting off and prevention of the electropain stimulation for three successive combinations (AR error). In another case the spatial stereotype of the experiment was altered by changing the place of the opening through which the animal avoided the stimulus (spatial remodeling). Intraperitoneal injection of GVS-111 (0.1 mg/kg/day) improved the learning, but the effect differed from experiment to experiment. Along with this, the dipeptide prevented AR disturbance during the error and quickened restoration of the habit in spatial remodeling. It was shown earlier that AR disorders during an error are prevented by anxiolytics and nootropic agents but during spatial remodeling only by nootropic agents. It may be assumed that the positive effect of GSV-111 on AR in functional disorders is due to its nootropic effect.

The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine.

The metabolism of a new piracetam analogue, the dipeptide cognitive enhancer N-phenylacetyl-L-prolylglycine ethyl ester (GVS-111) was studied in vivo. GVS-111 itself was not found in rat brain 1 h after 5 mg/kg i.p. administration up to limit of detection (LOD) under high performance liquid chromatography (HPLC) conditions. Three substances corresponding to the three possible GVS-111 metabolites, namely phenylacetic acid, prolylglycine and cyclo-prolylglycine, were found in experimental rat brain samples as well as in controls using HPLC, gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) methods. Only cyclo-prolylglycine concentration increased (2.5-fold) 1 h after GVS-111 administration. Cyclo-prolylglycine formation from GVS-111 in the presence of plasma and brain enzymes was shown in vitro. These data could be considered as evidence that GVS-111 is prodrug which converts in the body to cyclo-prolylglycine, and which is identical to the endogenous cyclopeptide that produces the nootropic activity.

The novel substituted acylproline-containing dipeptide, GVS-111, promotes the restoration of learning and memory impaired by bilateral frontal lobectomy in rats.

The present study investigated the potential benefit of the ethyl ester of N-phenylacetylprolylglycine (GVS-111) on the model of bilateral frontal lobectomy (BFL) in rats. The animals in Experiment 1 were trained in an active avoidance task and subsequently underwent BFL. The animals in Experiment 2 were first assessed in an open field and in a passive avoidance test before the BFL was performed. BFL dramatically decreased performance in the active avoidance test, disturbed habituation of horizontal activity in the open field and diminished the latency to enter the dark compartment in the passive avoidance test. GVS-111, administered in a dose of 0.5 mg/kg/day i.p. for 9 days following the operation, was found to improve performance in both active avoidance and passive avoidance and restored habituation of horizontal activity in the lobectomized animals.

[The significance of perinatal alcoholization and its withdrawal in the development of late cognitive disorders in rats]. / Zanchenie perinatal'noi alkogolizatsii i ee otmeny v razvitii otdalennykh kognitivnykh narushenii u krys.

To study the effect of perinatal alcoholization and its withdrawal on cognitive functions of rats, 25% ethanol solution was administered intragastrically: (1) over the whole period of the rat pregnancy in a dose of 5 g/kg/day; (2) from the Ist day of pregnancy to the 7th day after genera in a dose of 5 g/kg/day; (3) from the Ist day of pregnancy to the 2nd day after genera in a dose of 5 g/kg/day; and then in daily decreased doses (by 1g/kg) to the 7th day. A less pronounced increase in the rat mass and disturbances in maternal behavior (eating up the descendants) was observed for all alcoholization regimes. Alcoholization inhibited the eye opening, but did not affect the body mass increase and elementary inborn reflexes of descendants during the first three weeks of life, whereas in adult male descendants alcoholization deteriorated the ability to training and memory on the "open field" model and bilateral avoidance response. The cognitive disorders in descendants were more pronounced after abrupt withdrawal of ethanol directly after the birth and were minimal after gradual withdrawal of alcohol.

[The correction with nooglutil and L-pyroglutamyl-D-alanine amide of cognitive disorders in rats due to intrauterine hypoxia]. / Korrekstiia noogliutilom i amidom L-piroglutamil-D-alanina kognitivnykh narushenii u krys, vyzvannykh vnutriutrobnoi gipoksiei.

Novel nootropic compounds, nooglutyl (N-5-hydroxy(nicotinoyl)-L-glutamine acid, 25 mg/kg/day) and L-pyroglutamyl-D-alanine amide (1 mg/kg/day) administered intracutaneously from the 8th to 20th day of life prevent from movement hyperactivity in "open field", disturbances in ability to training and in memory in an alternate test and in tests of passive and active avoidance and normalize behavior of the adult mail rats (subjected to two-hour hypobaric hypoxia in on the 15-day of intrauterine life, vacuum corresponded to the height 8500 m) in-extrapolation avoidance test. Additionally, nooglutyl recovered the normal growth of rats in the first month of their life, prevented from deceleration of investigating behavior of adults animals and disturbances of the mink reflex in them.

[A comparative analysis of the effect of nootropic preparations with different chemical structures on the failure of the escape reaction in rats]. / Sravnitel'nyi analiz vliianiia nootropnykh preparatov razlichnoi khimicheskoi struktury na sboi reaktsii izbeganiia u krys.

The nootropic agents pyroglutamyl-D-alanine amide (TGS-20), mechlofenoxate, and mexidole versus piracetam were tested for their effects on the reversible impairments of cognitive brain functions, on the demolition of active avoidance responses in rats. TGS-20 (1 mg/kg/day) and mexidole (10 mg/kg/day) injected intraperitoneally 30 minutes prior to the experiment showed a normalizing effect in smaller doses than did piracetam (300 mg/kg/day). Mechlofenoxate (50 mg/kg/day) displayed a lower protective effect.