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Amphazide and tetramezine, two recently synthesized compounds with antidepressant and nootropic activities; were found to have dopamine-positive activity in animals injected with apomorphine, L-Dopa, or haloperidol. Amphazide expressed this activity in most tests only when given in multiple doses, whereas tetramezine expressed it well even after a single dose.Key Words: amphazide; tetramezine; dopamine-positive activity Dopaminergic (DA) structures are involved in memory processes, promoting the recall of what was learned long ago [13,15] and, when activated, contributing to effective restoration of forgotten habits [15]. There is evidence that the DA system is implicated in mediating the effects of certain antidepressants [1,3].The purpose of this study was to investigate how central DA structures might be influenced by two recently synthesized compounds with antidepressant and nootropic activities --amphazide, which is a hydrazide of phosphorylated carboxylic acids, and tetramezine, which is a diaziridine derivative. MATERIALS AND METHODSThe study was conducted on 170 random-bred mice (body weight 17-22 g) and 50 random-bred rats (body weight 150-200 g).Amphazide and tetramezine (TM) were injected intraperitoneally at 90 mg/kg body weight either once or ten times once daily, and their effects on apomorphine-induced hypothermia and stereotypy, LDopa-induced hypothermia and alterations in exploratory and motor activities, and haloperidol-induced catalepsy were evaluated. State Medical University, KazanHypothermia was produced in mice by a subcutaneous injection of apomorphine at 25 mg/kg, and their body temperature was recorded with an electric thermometer 1 and 2 h postinjection.The total duration of sterotypy and the intensities of its components (licking, sniffing, and gnawing) were measured in rats 1 h after a subcutaneous injection of apomorphine at 20 mg/kg. Skin temperature and exploratory and motor activities (the number of holes explored and of lines crossed in an open field) were recorded in mice 1 h after a subcutaneous injection of L-Dopa at 150 mg/kg.The severity of catalepsy was evaluated by the ability of mice to retain an awkward posture (with the hind legs on a support 30 mm high and the forelegs on the table) for 60 sec at 10, 60, and 120 min after haloperidol injection at 5 mg/kg.The results were statistically analyzed by Student's t test. RESULTSAmphazide potentiated the effects of apomorphine only in multiple doses, enhancing the hypothermia in mice (Fig. 1) and prolonging the stereotypy in rats (Table 1); the recording of individual stereotypy components in rats showed longer sniffing times in comparison with the control group. In contrast, TM
Age-related development of behavioral disorders in transgenic mice with modeled Alzheimer's disease carrying V6S3-Tg(APP695)85Dbo Tg(PSENI)85Dbo) genotype was assessed at the age of 7.5, 10 and 20 months in the following tests: open-field, plus maze, T-maze, conditioned passive avoidance response, rotarod, conflict situation with water deprivation, behavioral despair, and arecoline tremor. The main behavioral disorder in transgenic mice at all observation terms was memory impairment in conditioning with positive (but not negative) reinforcement. At the age of 7.5 and 10 months, transgenic mice also showed signs of nonspecific excitement and anxiety, depression-like state, and symptoms of cholinergic deficit. Our results suggest that appropriate age for behavioral tests in studies of effects of potential anti-Alzheimer drugs in transgenic V6S3-Tg(APP695)85Dbo Tg(PSENI)85Dbo) mice is 7.5-10 months.
Introduction. Behavioral methods on laboratory animals are recognized as the main approach in studying the activity of potential psychotropic drugs and allow us to evaluate the main effects of new compounds, increase the possibility of predicting a successful outcome of future clinical trials.Text. This review article analyzes the main modern behavioral models in rodents that are widely used for screening and studying the pharmacological activity of potential psychotropic drugs. The advantages and disadvantages of each test are highlighted and complexes of behavioral methods are demonstrated that most conclusively confirm the reproducibility of the results obtained in clinical trials. The description and evaluation of behavioral methods that characterize the state of anxiety, which are used to screen for new compounds with anxiolytic activity (tests «Open field», «Dark-light chamber», «Elevated plus maze», «Sequence of rays»). The range of tests used to study cognitive functions and memory processes is widely presented (various mazes – T-shaped, U-shaped, radial maze, Barnes maze, E-maze; water mazes – Morris, T-maze) with a description of a comparative analysis and necessary conditions that ensure the reliability of information. An important direction in the field of behavioral pharmacology is the modeling of violations of social behavior and the study of approaches for its correction – the main methods necessary for the study of social behavior are presented in the review by the tests «Three-chamber social test», «Open field» extended test, etc.Conclusion. Behavioral pharmacology dictates the need for close interaction between preclinical and clinical stages of research in the framework of the development of translational medicine and the development of approaches that provide evidence for the reproducibility of the results obtained in clinical trials. It is also necessary to improve existing and develop new behavioral models of mental disorders and to search for new ways to study the mechanisms of formation of behavioral disorders.
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