Method for detecting psychotropic activity of drug and drug-free substances. RU patent 2506649.
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| Method for combined tadalafil and l-norvaline correction of l-name induced nitrogen oxide deficiency in experiment / 2500040 Nitrogen oxide deficiency is simulated by the daily 7-day intraperitoneal introduction of N-nitro-L-arginine methyl ester 25 mg/kg into experimental Wistar male rats. The nitrogen oxide deficiency is corrected by the simultaneous 7-day intragastric introduction of a combination of tadalafil 0.09 mg/kg and L-norvaline 10 mg/kg once a day. |
| Method for simulating primary biliary cirrhosis / 2500039 Primary biliary cirrhosis is simulated by introducing 45-50% alcoholic solution of picryl sulfonic acid 0.08-0.12 ml into rat's bulbar duodenal lumen and terminal ileum every 5-10 minutes. The primary biliary cirrhosis is diagnosed 1-1.5 months later. |
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 Method and device for studying transosseous osteosynthesis model stiffness / 2246139Method involves studying transverse longitudinal and rotation stiffness characteristics. The studies are carried out step-by-step from the first order units to complete external fixation apparatus structure. The device has frame and is provided with calibration loads, wire rope, displacement indicators, strip for fastening to loading end of bone imitator fragment, beam for fixing displacement indicators, beams having unit for modeling longitudinal and transverse loadings. The frame is manufactured as parallelepiped. The fixing panel has openings for bone imitator, for fixing external fixation apparatus and yoke connection union and is fixed in end face part of the frame. Beam for fixing displacement indicators has longitudinal slit for fixing the indicators and arranging them on lateral slots in frame base. The beams having unit for modeling rotational, longitudinal and transverse loadings are arranged on lateral frame sides on lateral slots in base. |
 Method for experimental modeling urinary calculosis / 2248045The present innovation deals with modeling urinary calculosis in rats due to injecting intraperitoneally 60%-glucose solution at 1 ml/100 g animal body weight twice daily for 2 mo. The method is very simple and enables to achieve lithogenesis in 25% experimental animals. |
| Method for applying wave action to pathogenic microorganisms, viruses and tumor cells in experiment / 2250788 Method involves using Hann diode crystal with proper frequencies of pathogenic microorganisms and cells during their death period or during the stimulating factors action period being applied. |
 Method for modeling hypoxia with hypercapnia in animals / 2251158Hypoxia with hypercapnia should be modeled due to creating a closed system of inhaled air circulation. Air enters lungs out of hermetically sealed reservoir and at expiration returns back. The process of recirculation is supplied with an apparatus of artificial pulmonary ventilation. The innovation suggested provides steadiness in development of hypoxia with hypercapnia excluding the development of stressor reaction. Conditions should be created to carry out any manipulations with an animal in the course of an experiment. |
| Method for obtaining parodontitis model / 2252009 The present innovation should be carried out for the purpose to study ethiology and pathogenesis of parodontitis. One should affect with emotional stress in experimental animals (mature rats) due to placing 10-11 experimental animals into the cage at area of 0.018 sq. cm/animal. Before placing into the cage one should create artificial dental plaque around the cervix of the upper and lower incisors with the help of stomatological cement for every experimental animal. In the course of modeling all experimental animals should eat paste-like food. The method enables to shorten terms for obtaining the model desired and increase its similarity with pathomorphological manifestations of human parodontitis. |
 Acupuncture point electric model device / 2252743Device has input first variable resistor, capacitor and permanent resistor. Permanent resistor is connected to arm second and third variable resistors. Second ends of variable resistors are connected with motionless contacts of polarized relay. Movable contact of relay is connected to common bus. Input of device is connected to amplifier which has output connected with control wiring of polarized relay. Second end of wiring is connected with common bus. Device is intended for electrical modeling of balanced and misbalanced conditions of acupuncture point at electropunctural action with unlike-poled signals due to liquidation mutual errors at any circuit of opposite arms of the device. Values of active resistances can be installed independently at any arm of device. |
| Method for modeling hypoxic encephalopathy / 2253152 Laboratory animals should be once injected intraperitoneally or intravenously with phenylhydrazine at the dosage of 100-150 mg/kg. |
| Method for modeling chronic toxic nephropathy / 2253153 At studying the mechanisms of heavy metals toxic action, in particular, cadmium upon renal function, it is suggested to introduce cadmium sulfate solution into stomach once daily for 2 mo at the dosage of 0.5 mg/kg, on conversion to metal, where cadmium corresponds to 0.5 mg per 1 ml solution. The present innovation enables to study the pathology in dynamics of development and elaborate and searching preparations for treating and preventing chronic toxic nephropathy. |
| Method for stopping carcinoma cells division in a biological object / 2253903 Method involves exposing cell or cell group to external power source. At least two electrodes are introduced before treating the cells. One of electrodes is set on cytoplasmatic external cell membrane surface and the other one cell membrane and membrane potential value is measured. External electric voltage source is connected to the introduced electrodes oppositely in polarity with cell membrane potential difference value being not less than cell membrane potential. |
FIELD: medicine.
SUBSTANCE: invention refers to medicine, in particular to experimental pharmacology. Detecting the psychotropic properties of the analysed substances is ensured by modelling an emotional-physical stress situation reached by placing the animal into a cylinder with cold water. That is followed by recording a time for solving and fulfilling the task to escape from the cylinder with using the presented rescue aids (lath, stairs and cord) in the cylinder. A percentage probability of solving the task is calculated. Indices characterising the psychoemotional and locomotor effect of the analysed substances are calculated by specific formulas.
EFFECT: method is technically simple, low-cost, has a high level of reproducibility, enables detecting a psychosedative and psychostimulating effect of the analysed substance with low cost and high probability.
1 dwg, 3 tbl, 2 ex
The invention relates to the field of experimental pharmacology and medicine and can be used to identify psychotropic properties of the studied medicinal and non-medicinal substances.
The existing methods of evaluation of behavioral reactions of laboratory animals for the purposes of pharmacologic screening ( L.V. Biological bases of rational activity: Evolutionary and physiological-genetic aspects of behavior./... - M, 1977.; VS, Antipov, V.V., B.I. Davydov, Ushakov I.B. // Izv. SSSR, ser. Biol. - 1982. - №2. - .284-287) have a number of limitations that are associated with high costs of time to conduct an experiment, a large variability in the results obtained in time for various species of animals and low probability of their manifestations among the population of animals.
To assess activity medicinal substances in relation to hypoxia of the brain known method of bilateral occlusion of arteries - ligation of the common carotid arteries under anesthesia (Mirzoyan R.S. Methodical instructions on the experimental study of drugs for the treatment of cerebrovascular disease and migraines. Guide on experimental (pre-clinical) study of new pharmacological substances./ Under the General editorship of ... - 2-e Izd., Rev. and extra - M: JSC «Publishing house «Medicine», 2005. - 832 C.). Method is appropriate to study the influence of substances on the brain blood circulation and is not intended to assess other manifestations of psychotropic activity of studied substances.
To study the influence of different factors (including medicinal substances) on the neurological status of the animals shall estimate the total 12-point system. Each reaction is estimated from the maximum number of points equal to 2-m - normal (2 points), low (1 point) or absent (0 points) reflexes. Evaluate the following reflexes - reaction tail and paws, startle response to an auditory stimulus, grasping paws, rolling, corneal reflex (Б Ya Methodology and main experiments on the study of brain and behavior./.Б, .Б, .../Lane. from English. ... - M, Vysshaya SHKOLA, 1991. - 399 C.).
Known method and the method of determination of psychotropic properties of medicinal substances in animals, which consists in the fact, that after the introduction of the studied substance exercise suspension of the animal's tail in a special device, which is equipped with a sensor sensitive to the vertical displacement of the animal's body, which is a manifestation of anxiety and agitation (FR2577791 (A1). Method and device for evaluating the psychotropic effects of medicinal substances on animals /Stem Lucien/ A01K 29/00; A61B 5/11; (IPC1-7): A61B 10/00; A61B 5/16; A61K 49/00; G01N 33/15).
Indicators of locomotor activity using or . For example, at use of the device «Ugo Basile» (Italy) rat is loaded into the chamber size 37 x 27 x 27 cm, with a transparent top and the floors of the 30 steel bars, placed at equal distances and isolated from each other. Registration of results is carried out with the help of the attached printer. Motor activity register within 5 min and assessed in conventional units. Devices to assess the impact mainly on the locomotor activity of animals, besides serious drawback is the high cost of these devices.
For the evaluation of free rat behavior known use of the test «open field». For this animal is placed on a certain fixed time, for example 3 min, well-lighted «field» in the Manege square of various sizes. The standard model fields for rats is a Manege square of plywood in the size 80 x 80 cm, the legs of the length 15,0 see the Surface of the arena is divided into 16 painted and unpainted squares with side 20 cm, alternate in a checkerboard fashion. In the center of each square is a hole the size of 3.8 cm - «mink». Known also, various modifications of the arenas in size and form. Horizontal activity is an index of locomotion - take into account the number of clicks animals squares. Vertical activity (or «front») is defined as the number climbs on his hind legs, with full isolation of both the front limbs from the bottom - criterion is indicative of the reaction. Recorded number of fecal bolus reflects autonomic effects of emotional reaction to fear caused by placing the animal in the unknown environment. Mink reflex is determined by the number of in the «hole» - describes the spontaneous research activities. The number of acts of grooming, i.e. and scratching characterizes the emotional status. Fixed time of observation (standard recommended time - 3-10 minutes, if necessary, may be increased or decreased), consider using a stopwatch (Experimental modeling and laboratory evaluation of adaptive reactions of the organism /.. [and others]. - Chelyabinsk: , 2000. - 167 C.). Method allows to estimate the effects on motor activity and General emotional status of the animal.
Known method involving the use of uplifted cruciform labyrinth. Most of its common option is the installation consisting of 4 crosswise diverging from the Central site of the bags (two public and two private). The animal is placed on the Central platform of the head to the open sleeve, for a certain period of time (from 5 min with intervals re) register the stay in the open and closed sleeves, Central location, number of logins public and private support the latent period of the first entry in the open sleeve. Recorded also the number of urinary and fecal bolus, the number of vertical racks. Emotional activity assessed by the number of fecal bolus and urination. Motor activity assessed on the overall number of visits in open and closed sleeves and vertical racks. The model is intended to assess the anxiolytic activity of the investigated substances, substances with an anxiolytic effect of increasing the number of visits in the light of the sleeve and the time spent in them without a General increase in the number of visits (Voronin T.A., S.B. Seredenin Kiryukhina trankviliziruyuschego (anxiolytic) actions of pharmacological substances./Manual experimental (pre-clinical) study of new pharmacological substances./ General Ed. ... - 2-e Izd., Rev. and extra - M: JSC «Publishing house «Medicine», 2005. - 832 C.).
Proposed for laboratory animals (Application for invention RU 92000559, IPC 61 5/00), which according to the description can be used during the investigation of drugs on psychotropic activity. According to the description for improving productivity and quality research, and extension of functional capabilities , for laboratory animal entered the third OPTRON pair and host registration, made in the form of the electronic unit.
To identify the properties of drugs with the alleged psychotropic effect known method (Pat. EN 2328038, IPC G09B 23/28), which consists in the formation of inbred mice psychoemotional disorders in a situation of social conflict. To identify therapeutic properties of the drug in animals form a depressed in conditions of chronic social conflict within 20-30 days, then the premises of the animals in a comfortable stay and a daily appointment of an investigational drug for at least 2 weeks. To identify the protective properties of the drug in animals within 5-7 days form the contrasting types of social behavior and their background, daily enter the investigational drug within 2 weeks.
A method is proposed (Application for invention RU 2001103771, 61 5/11) identifying psychotropic properties of substances, including premises for animals under the influence of investigated material, in camera, quantitative assessment of integrative indicators of search behaviour in experimental animals, differs in that the assessment is carried out at different motivations. As the experimental setup used problematic Luggage. Device for detecting psychotropic properties of pharmaceutical products, including the problem of the camera, the Registrar, the different fact that the electrode floor is fitted with a removable flooring, drinkers and feeders are put outside of the camera.
There is a method of modeling disorder, which according to the description can be used when checking for new psychotropic drugs (Pat. EN 2311691, IPC G09B 23/28). The method consists in that in rodents determine the pain threshold (BP) sensitivity and endurance (Б and PPO). Then 20-30 minutes before stressor exposure to spend injection funds. 15-25 minutes just before stressor exposure to re-measure the Б and the PPO and subjected rodents emotional stress for 4-6 minutes. The register, the total duration of immobilization. After 2-10 minutes after the stress exposure to re-define Б and the PPO. By the nature of the combination of the duration of immobilization and changes Б and the PPO is judged on the sensitivity of rodents to stress and severity of depersonalization. On changing the PSU between the first and second their dimensions are judged on the impact of the drug on pain perception, and between the second and third dimensions BP - severity of analgesia from stress. According to the description of the method allows to study the mechanisms of formation of disorders and to develop methods of its treatment.
Known plant « deliverance», designed according to the description of [the Internet-site of OOO «NPK Open Science», http://www.openscience.ru/index.php?page=ts&item=004], for the study of cognitive functions rodents in the conditions of acute stress and allows to estimate: individual differences in cognitive style of the problem of search of a way of deliverance from acute stress situations); formation of cognitive functions in ontogenesis; the impact of pharmacologically active substances. According to the description, the installation is intended for testing of rats and represents the inner cylinder made of clear acrylic plastic, external container of white polypropylene, steel mounting keep the cylinder in the center of the container. To test the animals need water availability (22 OC) in an external capacity, cylinder should be immersed in water of 2.5 cm). Including, according to the description setting suitable for screening anxiolytics, psychostimulants, neuroleptics, atypical tranquilizers, antidepressants, neuroprotection.
The closest to the present invention is a known test «forced swimming». Principle of the test is reduced to the evaluation of the life expectancy of animals in the conditions of the physical loading (swimming) at a relatively low temperature of water (17-20 degrees below average body temperature). The test is performed on mice and rats. Animals are forced to swim at low temperature water for 30 minutes. Register the voyage until the occurrence of death and the estimated mortality rate (per cent of total mice) during the observation period. For the formulation of the test in mice use glass chromatographic camera about the size of 29 x 19 x 40.5 cm or plastic buckets similar size. During the test the forced swimming in mice height of the water column must be at least 20 see For the test «forced swimming» on rats used tank higher-capacity, for example, according to the description, metal tank circular crosssection, of a diameter of 63 cm, a height of 72 see the Water column, no less than 50 cm, height of the tank, which is not occupied with water for at least 22 see Water temperature for the «forced swimming» rats ranges 17-18°C. In the rest of the test is the same as described above technique for mice. Subject to the above conditions, according to the authors, the mortality of rats is 93,87% for 30-minute observation period, the average latency of death equals 18,88±2,2 minutes (Experimental modeling and laboratory evaluation of adaptive reactions of the organism /.. [and others]. - Chelyabinsk: , 2000. - 167 C.). The specified parameters of the test should be considered as disadvantages, as, firstly, according to the description, the model involves a high percentage of death of the animals that does not quite meet modern principles of humane treatment of animals, and, in addition, increases the consumption of animals to conduct an experiment, respectively, increasing costs; second, the indicated period of observation is quite lengthy, which increases the cost and time to conduct experiments. According to the description, the forced swimming test is designed for integral evaluation mechanisms resistant (i.e. stress) adaptation strategy, that is not intended directly for the detection of psychotropic activity of studied substances.
Object of the present invention is to provide a method suitable for screening, and the study of the pharmacological activity of substances with potential psychotropic properties.
The technical result consists in the speed, simplicity and way.
The technical result is achieved by the method of revealing of psychotropic activity medicinal and non-medicinal substances consists of modeling emotional and physical stress of the situation, achieved placing animals in glass cylinder filled with cold water, the first sight of the means of salvation in the form of Reiki, stairs or ropes installed in the cylinder, the second presentation of the means of salvation after a specified period of time, the check-in time from the moment of immersion in water up to the moment of choice of the means of salvation (time finding solutions to the tasks Hungary) and time from the moment of choice of the means of salvation before entering the output pad button above the cylinder with water (implementation of the solution of the task VVR), counting the number of animals who have successfully completed the task and calculate the probability of a solution to (OCR) by the formula
where n is the number of animals in the group who have successfully completed the task, N is the total number of animals in the group subjected to the experiment, calculating index of psychoemotional influence (idea) by the formula
where BHP o1 - time finding solutions to the tasks at the first sight the means of salvation in the experimental group; Hungary O2 - time finding solutions to the tasks at the subsequent after the first after a specified period of time (re) presentation of the means of salvation in the experimental group; BP3 o1-the probability of solving the task in percentage (see above) at the first sight the means of salvation in the experimental group; car-O2 - probability of solving the task in percentage (see above) during the repeated presentation of the means of salvation in the experimental group; Hungary Q1 - time finding solutions to the tasks at the first sight the means of salvation in the control group; Hungary K2 - time finding solutions to the tasks at repeated presentation of the means of salvation in the control group; VRZ K1 - the probability of solving the task in the percentage at the first sight the means of salvation in the control group; VRZ K2 - the probability of solving the task in the percentage when you re-presentation of the means of salvation in the control group,
index-motor-motor impact (IDD) by the formula
where VVR O1 - time execution of the decision of tasks at the first sight the means of salvation in the experimental group; WWR - O2-time execution of the decision of tasks in a subsequent after the first timeout (re) presentation of the means of salvation in the experimental group; car-O1 - the probability of solving the task in percentage (see above) at the first sight the means of salvation in the experimental group; car-O2 - probability of solving the task in percentage (see above) during the repeated presentation of the means of salvation in the experimental group; VVR Q1 - time execution of the decision of tasks at the first sight the means of salvation in the control group; VVR K2 - implementation of the solution of the problem when you re-presentation of the means of salvation in the control group; VRZ K1 - the probability of a decision of a task in percentage at the first sight the means of salvation in the control group; VRZ K2 - the probability of solving the task in the percentage when you re-presentation of the means of salvation in the control group,
moreover, if the IAP<1.0 the studied substance characterized by the presence of psychostimulant effects and indicates the probability of having , tonic, , nootropic activity of the studied substance, IAP>1,0 - characterized by the presence of effect and indicates the probability of having a sedative, neurotic, , deprimating activity of the studied substances, if an IVA<1.0 then examined the substance has the ability to increase the motor activity and indicates the probability of having , effects of the studied substance, an IVA>1,0-describes the ability of a substance to reduce locomotor activity and indicates the probability of having , miorelaksirutego, effects of the studied substance.
Modeling of emotional and physical stress of the situation can be done at the facility proposed by the group of authors (.., .., ... Experimental model of heuristics in rats for the pharmacological screening. Pharmacology and toxicology. 1989, .52, №4, pp.96-99) with modifications.
Figure 1 presents a diagram of the device; figure 2 - table 1-the preservation of the memory about the found solution tasks in conditions of the need to change the stereotype (note: * - p<0.05 significance of differences in comparison with the initial data for the group; legend: SAS, % - probability of solving the task in percentage; the means of salvation: 1 rail, staircase, 2 - rope; 1+1 - rake staircase on the first and second presentation - without change of salvation, 1+2 - rake staircase at the first sight and rope at the second presentation - a change of the way of salvation; 2+2 - rope at the first and second presentation - without change of salvation)in figure 3 table 2 - impact workout for speed challenge in terms of the need to change the stereotype (note: use the legend: the means of salvation: 1 rail, staircase, 2 - rope; Hungary - time finding solutions to the tasks of the VVR - time execution of the decision of tasks, VRZ, % - solution of the problem in probability percent); figure 4 table 3 - evaluation of psychotropic activity the known substances with the help of experimental modeling tasks search heuristics (note: * - p<0.05 to the control group, ** - p<0.05 to initial background).
Device for detection of psychotropic activity of substances using a heuristic model of the process of finding animals solutions to the task of salvation consists of a glass cylinder 1 and a watered 2, output pad 3, canopy 4, Reiki or ladder 5, crosses for fixing ropes 6, ropes 7, tray 8 with the walls of 12, placed in the tray 9, the upper chambers of the cylinder 10, the lower chamber for 11, the bottom of the tray 13 upper trough bottom 14.
To maintain a constant desired water temperature glass cylinder is placed in the tray 8 camera located at him 9. The tray is made of sheets of foam polystyrene with the walls of 12 thickness 2,0 see Tray consists of a lower chamber 11 for and the upper chambers of 10 for the cylinder with water, the sizes of tray - 15.0 cm height from the bottom of the outer dimension of the bottom 29,0 x 29,0 see Camera for has two bottom - top bottom 13 and bottom bottom 14. In a closed form Luggage for represents a with the size of the bottom 29,0 x 29,0 cm, top-bottom 25,0 x 25.0 cm and a height of 7,5 cm, sheet top-bottom has a through slot in the middle with the size of 1.5 x 2,0 x 2.0 cm for easy retrieval sheet top-bottom. The upper chamber for the cylinder has external walls, height 7,5 cm from the top of the bottom, the bottom of the camera for the cylinder is sheet the top of the bottom of the camera for with dimensions 25,0 x 25,0 see Tray set on a horizontal surface, remove the top sheet of the bottom with a camera by seizing of a finger through the slot in the camera at the bottom bottom placed , put a sheet of top-bottom back, then on top bottom set top cylinder and fill it with water. Use any famous brand, manufactured industrially for example reusable MHD-1 dimensions 165 x 95 x 33 mm Before using frozen in a freezer domestic refrigerator at a temperature of minus 18,0°C + 2.0°15-24 hours at a time, then incubated at room temperature (+20,0±2,0 OC) 1 hour and then they put it in the tray under the top bottom of the cell for .
Water is poured into the cylinder to the level of 15.0 cm from the bottom. This level of water eliminates the possibility of contact limbs of an animal from the bottom of the cylinder and thus avoiding the stressful situation of necessity swimming in cold water.
The cylinder is lowered proposed means of salvation - rake 5, ladder or rope 7. Rake and stairs made of wood, cotton rope. One end of the ladder or rake rest on the bottom of the cylinder angle of 60o and fixed on the opposite edge of it to the output area. Output Playground 3 covered mounted on it canopy 4 that mimics the «hole». Rope 7 one end snaps to the center of the cross 6 from reek, placed on top of the cylinder, the other end of the rope dangle above the surface of the water filling the cylinder.
Experimental animal is placed in a tube with cold water and conducting monitoring, recording the time of the decision and task execution leave the cylinder.
The observation time is 2 minutes. If after 2 minutes the animal has not complied with the problem of saving (i.e. has not chosen a means of salvation and continues to swim or sink), animal extract from the cylinder and consider this result as not completing the task. The number of such animals, not having performed the task is subtracted from the total number of animals in the group receiving a number of animals who have successfully completed the task.
To study the ability to change the stereotype way of solving a problem animals trained to leave the barrel with cold water using one of the means of salvation daily for 3 days. On the 4th day of the animals provide the possibility of solving a problem using previously not subject. Saving the memory about the solved task judged by the speed of its decision in the second of its presentation 15 min, 2, 4, 6 hours, 1 and 7 days after the first experiment.
Evaluation criteria:
- the time for solving problem (s) - next conditionally indicated by the abbreviation Hungary, the time from the moment of submersion in water up to the moment of choice of the means of salvation (rope ladder or rake). Time measured using a stopwatch. Characterizes the emotional status and functions of the higher nervous activity of the test animal.
- implementation of the solution of problem (s - next conditionally indicated by the abbreviation VVR, the time from the moment of choice of the means of salvation before entering the output pad button above the cylinder of water. Time measured using a stopwatch. Describes mainly the motor status, including muscle tone.
the likelihood, the solution to (%) - next conditionally indicated by the abbreviation of the SAS, the number of animals who have successfully completed the task in percentage of the total number of animals in the group, calculated by the formula
where 3 - the probability of solving the task in percentage, n is the number of animals in the group who have successfully completed the task, N is the total number of animals in the group subjected to the experiment.
For data processing and data interpretation is calculated indexes: Index of psychoemotional influence (SPD) and the Index of motor-motor impact (IDD) by the formulas (2) and (3):
Index psychoemotional influence characterizes the impact of studied substance on the General psycho-emotional status and evaluated by the ability to change the time spent animal on the heuristic search process solutions to the task of salvation in the dynamics of the first and subsequent presentation of possible solutions to a problem.
Criteria for the assessment of the values of the Index of motor-motor impact: an IVA<1,0 - describes the ability of a substance to improve motor activity; indicates the probability of having , effects of the studied substance. An IVA>1,0 characterizes the ability to reduce motor activity of the studied substance; indicates the probability of having , miorelaksirutego, effects of the studied substance.
Example 1
Originally approbation of the suitability of the proposed method by the study of behavioral reactions of healthy animals when heuristic search for solutions to the task of avoiding extreme situation. In this series of experiments, no matter animals is introduced, and assessed their behavioral reactions in the proposed model of the situation.
Experiments are conducted on 141 white outbred rats males weighing 220-260, the Animals were divided into groups depending on the purpose of the experiments with the observance of the principle pair analogues. The significance of differences between the received digital values from experimental groups was performed by Fisher method ( E.V. Computational methods of analysis and recognition of pathological processes. /... - HP, 1978).
It is established that in the group of healthy intact rats (control group) the average time for the decision of tasks on avoiding the stressful situation swimming in cold water with the help rejki or stairs essentially did not change and amounted to 40 animals in the average 90,7 with (78,2 to 103,2). The solution time by means of a rope was 155,2 with (131,1 to 179,3).
The probability of performing tasks corresponded 97,3% upon presentation of Reiki or stairs and 87,0% - rope. When re-testing in 15 min, once again getting into a similar situation, dogs were doing the same task in 3-5 times faster (table 1).
It is established that the memory about the found way to avoid extreme situation persisted for 7 days. The memory of the only possible solution of this problem was of a General nature with fixing the ultimate goal of behavioral reactions. Replacement of a subject of salvation (rejki on a rope), leading to a change in certain stereotype of action, virtually no impact on the result of the task execution (see table 1).
Daily for 3 days training can reduce the time that the rat leaves bowl of cold water with the help of the offered means of salvation, almost to a few seconds (table 2). Change of Reiki or stairs to rope in this situation did not have a material impact on the speed of implementation of behavioral reactions.
Reduction of time of the first decisions of the task was achieved by pre-exposure of the animal in cold water for 15 minutes, without the means of salvation, which increased the motivation of a quick search of optimum yield from the adverse stressful situation.
Proposed a more complex way of avoiding the extreme situation with the help of a rope pulls in time solution of the problem as compared to the case of a simpler way of achieving the goal (table 2), since the execution of exercises on a rope requires animal considerably more time than a rail or stairs. The daily training time for decision-making is reduced, but the difference between the situation with more and less complicated ways of achieving the goal remains the same (see table 2). This example proves the ability of the animals to predict the complexity and the final result of the activities prior to the commencement of behavior act. To heuristic decision of the animal comes fingering the light most possible ways to achieve the goal with further formation of a more complex sequence of the actions prior to the commencement of behavioral reactions.
Thus, the proposed method is suitable not only for studying the influence of different factors (including medicinal and non-medicinal substances) to the speed of the decision a relatively easy for rodents tasks, allowing you to determine the impact of various factors on motor function and overall mental status, but also a way suitable for assessing the impact of higher nervous activity and the ability to form a solid behavioral act with fixing the ultimate goal of action, which provides the opportunity to identify the influence on cognitive processes.
Example 2
In table 3 provides data on the influence of test-known substances, showing psychotropic activity, on the ability of animals to find and implement solutions to the task of avoiding the stressful situation.
It is established, that the use of chlorpromazine in a dose of 5 mg/kg of morphine doses of 5-10 mg/kg of sodium oxybutyrate at a dose of 250 mg/kg, there was a significant decrease in the number of animals successfully resolved the problem at the first sight (the probability of solving the problem is 55,5%, 60.0% and 80.0% respectively specified groups) at 100 percent of the solution for 2 min in biological control group (healthy animals, without the introduction of any medicinal substances). If a group of control animals with repeated testing (15 min after the decision of tasks on first sight) time to complete and the solution of the task reduced in 2-3 times, among the animals treated with chlorpromazine and morphine, the time for solving tasks remained almost at the source level, which indicates the ability of chlorpromazine and morphine hinder the formation of short-term memory of correctly found the solution to the task. Marked effect is most expressed in the introduction of morphine doses of 5.0-10.0 mg/kg To decrease the dose of morphine to 1.0 and 2.5 mg/kg never recorded adverse action of the drug, for a dose of 2.5 mg/kg revealed a significant time spent and the execution of the decision of tasks of the first and further testing of, respectively, the calculated values of the Index of psychomotor impact amounted to 1,949 Index-motor-motor impact 3,369. For sodium oxybutyrate at a dose of 250 mg/kg calculated values of the Index of psychomotor impact amounted to 2.253 Index-motor-motor impact 2,276. In case of reduction of the dose of sodium oxybutyrate (up to 100 mg/kg) in animals primarily recovered the ability to learn quickly leave the cylinder when the stress of the situation, although the time of the decision at the first sight in these conditions was significantly (in 2 times more, than in control rats (see table 3). Chlorpromazine dose of 5.0 mg/kg also caused increase in time spent and the time of execution of the decision of tasks, respectively Index psychomotor impact amounted to 4.04 the Index of motor-motor impact improvement of 11.84 that characterizes most pronounced dampening effect among the above drugs (see table 3).
When applying fenazepam in doses of 0.5-1 mg/kg was observed the same direction of change of behavioral reactions with increase in time spent and task execution, delay ability to solve the task for the first and repeated demand, the decrease in the number of animals who have successfully completed the task, which accordingly was reflected in higher values of the Index of psychomotor effects (was 1,609) and the Index of motor-motor impact (1,608) (see table 3).
Thus, chlorpromazine, morphine, sodium oxybutyrate and valium caused a reduction of psychomotor and motor activity, sharply reduced the ability of rats forming behavioral avoidance response stressful situation. The effect of drugs reduced the total number of animals capable to solve this problem.
The installed complex changes confirms the suitability of using the proposed method for evaluation of psychotropic activity of substances, as it is known, chlorpromazine, morphine, sodium oxybutyrate and valium have a pronounced (, ) effect and also cause inhibition of motor component of behavioral reactions, providing Central muscle relaxing effect [M.D. Mashkovsky Medicines: in 2 so - Vol.1. - 14-e Izd. Rev., Corr. and extra - M: Publishing house «New wave»: Publisher .Б., 2002. - 540 C.].
Amphetamine dose of 5 mg/kg caused increased, however motor activity of rats and eliminate almost all animals attempts to leave a bowl of cold water with the help of the proposed means of salvation - the number of animals who fulfilled the task at the first sight does not exceed 10.0%of the re - none of the animals of the experimental group was not able to perform the task (the probability of a solution of the task of 0.0%, calculating indices of repair). At doses of amphetamine 1-2 .5 mg/kg all animals solved the problem when it first presentation (the probability of a solution of the task 100,0%), but noted, lengthening the time as the adoption of decisions and the exercise, which is especially pays attention by repeated, after 15 minutes, the presentation of the same tasks, in addition, a reduction in the number of animals have successfully completed the task by decision before you re-80,0%, which indicates a reduction in ability to form short-term memory. Accordingly, these changes were expressed in the significant increase in Index values psychomotor effects (amounted to 4.62) and the Index of motor-motor impact (4,73) (see table 3). These facts demonstrate the suitability of the proposed method for evaluation of psychotropic activity, as it is known, phenaminum, has a stimulating effect on the Central nervous system and increases the ability to perform physical work in combination with the effect of subjective reduce the feeling of fatigue and eliminate feelings of fear [M.D. Mashkovsky Medicines: 2 T. - Vol.1. - 14-e Izd. Rev., Corr. and extra - M: Publishing house «New wave»: Publisher .Б., 2002. - 540 C.]that leads to impaired ability to implement targeted activities.
Caffeine doses of 5-10 mg/kg significantly reduced the time spent on the solution of the problem, but not have such a marked influence on the speed of its implementation, respectively, for a dose of 5.0 mg/kg calculated Index psychomotor impact was 0,965 and the Index of motor-motor impact 1,247 (see table 3). Thus, by means of the proposed method for evaluation of psychotropic activity confirmed famous for caffeine psychostimulant properties, the ability to stimulate the positive conditioned reflexes and improve motor activity [M.D. Mashkovsky Medicines: in 2 so - Vol.1. - 14-e Izd. Rev., Corr. and extra - M: Publishing house «New wave»: Publisher .Б., 2002. - 540 C.].
Piracetam dose 800,0 mg/kg caused a reduction in the time of stay of the decision of a task with only a slight increase run-time solution of the problem, a slight decrease in the probability of execution of the decision of a task group, respectively, revealed a decrease in the values of the Index of psychomotor effects (was 0,955) with an increase of the Index of motor-motor impact (0,983), these changes are explained by a large dose of pyracetam, and it is known that in large doses pyracetam increases GABA- brake processes.
Piracetam in the dose of 400.0 mg/kg reducing the time that the decision and the time of execution of the decision of the problem when 100,0% it is executed at the first and subsequent sight, respectively, revealed a decrease in the values of the Index of psychomotor effects (was 0,955) and the Index of motor-motor impact (0,983) (see table 3). Low severity of the changes is explained by the introduction of a single pyracetam (according to the objectives of the experience, as for all other substances), and it is known that sufficient efficiency usually develops in 2-3 weeks of daily use. The established changes demonstrate the suitability of the proposed method for evaluation of psychotropic activity, as it is known, piracetam increases integrative and cognitive brain activity [M.D. Mashkovsky Medicines: in 2 so - Vol.1. - 14-e Izd. Rev., Corr. and extra - M: Publishing house «New wave»: Publisher .Б., 2002. - 540 C.].
Strychnine in doses of 0.1-0.2 mg/kg caused a slight decrease in time spent and the execution of the decision of tasks in first test, however, reduced the percentage of the quantity of animals have successfully completed the task (see table 3), respectively showed an increase of the values of the Index of psychomotor effects (was 1,108) and the Index of motor-motor impact (1,067). The established changes demonstrate the suitability of the proposed method for evaluation of psychotropic , as it is known, that strychnine in low doses skeletnuu tones muscles, but mainly facilitates the conduction of impulses mainly in the synapses of the spinal cord [M.D. Mashkovsky Medicines: in 2 so - Vol.1. - 14-e Izd. Rev., Corr. and extra - M: Publishing house «New wave»: Publisher .Б., 2002. - 540 C.]without affecting significantly the overall mental status.
The developed method for detection of psychotropic activity of substances, performed in rats using a heuristic model of the process of finding animals decision of tasks on the rescue of emotional and physical extreme situation allows assessment of the impact of potential psychotropic substances of higher nervous activity animals on the formation of solid behavioral response in solving the problem at the first and subsequent presentation.
Method for detection of psychotropic activity of medicinal and non-medicinal substances is in the modelling of emotional and physical stress of the situation, achieved placing animals in glass cylinder filled with cold water, the temperature is constant, the first sight of the means of salvation in the form of Reiki, a ladder or a rope, installed in the cylinder, the second presentation of the means of salvation after a specified period of time, the check-in time from the moment of immersion in water up to the moment of choice of the means of salvation (time finding solutions to the tasks Hungary) and time from the moment of the selection of the means of salvation before entering the output pad button above the cylinder with water (implementation of the solution of the task VVR), counting the number of animals who have successfully completed the task and calculate the probability of a solution to (OCR) by the formula
where n is the number of animals in the group who have successfully completed the task, N is the total number of animals in the group subjected to the experiment, calculating index of psychoemotional influence (idea) by the formula
where BHP o1 - time finding solutions to the tasks at the first sight the means of salvation in the experimental group; Hungary O2 - time finding solutions to the tasks when you later after the first after a specified period of time (re) presentation of the means of salvation in the experimental group; car-O1 - the probability of solving the task in percentage (see above) at the first sight the means of salvation in the experimental group; car-O2 - probability of solving the task in percentage (see above) during the repeated presentation of the means of salvation in the experimental group; Hungary Q1 - time finding solutions to the tasks at the first sight the means of salvation in the control group; Hungary K2 - time finding solutions to the tasks at repeated presentation of the means of salvation in the control group; VRZ Q1 - probability solution of the problem in percentage at the first sight the means of salvation in the control group; VRZ K2 - the probability of solving the task in the percentage when you re-presentation of the means of salvation in the control group, and the index of motor-motor impact (IDD) by the formula
where BBP o1 - time execution of the decision of tasks at the first sight the means of salvation in the experimental group; WWR - O2-time execution of the decision of tasks in subsequent after the first after a specified period of time (re) presentation of the means of salvation in the experimental group; car-O1 - the probability of solving the task in percentage (see above) at the first sight the means of salvation in the experimental group; car-O2 - probability of solving the task in percentage (see above) during the repeated presentation of the means of salvation in the experimental group; VVR Q1 - time execution of the decision of tasks at the first sight the means of salvation in the control group; VVR K2 - implementation of the solution of the problem when you re-presentation of the means of salvation in the control group; VRZ K1 - the probability of solving the task in the percentage at the first sight the means of salvation in the control group; VRZ K2 - the probability of solving the task in the percentage when you re-presentation of the means of salvation in the control group, and, if children's suffrage<1.0 the studied substance characterized by the presence of psychostimulant effects and indicates the probability of having , tonic, , nootropic activity of the studied substance, IAP>1,0 - the studied substance is characterized by the presence effect and indicates the probability of having a sedative, neurotic, , deprimating activity of the studied substance, an IVA<1.0 then examined the substance has the ability to increase the motor activity and indicates the probability of having , effects of the studied substance, an IVA>1,0 - the studied substance is characterized by the ability to reduce locomotor activity and indicates the probability of having , miorelaksirutego, effects of the studied substance.