The effects of amitriptyline (10 mg/kg), melipramine (10 mg/kg), and fluoxetine (5 mg/kg) on the acquisition of conditioned active avoidance responses and their spatial alteration in rats were studied. During the acquisition of avoidance, a passage in the partition was open, adjacent to the rear wall of the shuttle chamber. On the 5th experimental day after the end of the training, this distal opening was closed and the proximal one was opened, after which avoidance performance under changed conditions was tested for 20 trials. Melipramine and amitriptyline accelerated the acquisition of avoidance responses. Changing the location of the opening disrupted the learned skill, especially in the control animals. Melipramine and fluoxetine statistically significantly (in contrast to amitriptyline) accelerated the recovery of the level of avoidance. The positive effect of melipramine and fluoxetine is explained by a psychostimulating component in their spectrum. The inability of amitriptyline to produce a significant effect in this model is due to its psychosedative properties. The data obtained allow us to conclude that the acquisition of the active conditioned avoidance responses and their spatial modification can be used to analyze the antidepressant activity of pharmacological agents.

The significant destructive changes in ultrastructure of hepatocytes from laboratory mice kept in different vivariums in Moscow and fed with dry laboratory animal diets acquired from different domestic manufacturers that were not standardized for initial products were demonstrated using electron microscopy. Furthermore, disruption in the ultrastructure of liver parenchymal cells occurred regardless of the animal status (SPF or conventional), conditions of various vivariums, as well as the feed manufacturer. At the same time, studies on ultrastructure of liver hepatocytes from mice kept in the Charles River Laboratory facilities in Germany and fed with the Altromin Spezialfutter laboratory animal diet (GmbH & Co., Germany) that was produced using quality control of ingredients did not reveal destructive changes in the internal ultrastructure of hepatocytes. However, if these mice were later fed with the food produced in local manufactures, changes in the structure of liver cells developed after 2 months. Thus, feeding with dry diet from the domestic producers of an unspecified composition causes significant changes in the ultrastructure of hepatocytes in control animals, reflecting the development of some pathological processes in the body.

According to one hypothesis, Parkinson’s disease pathogenesis is largely caused by dopamine catabolism that is catalyzed on mitochondrial membranes by monoamine oxidase. Reactive oxygen species are formed as a byproduct of these reactions, which can lead to mitochondrial damage followed by cell degeneration and death. In this study, we investigated the effects of administration of the mitochondrial antioxidant SkQ1 on biochemical, immunohistochemical, and behavioral parameters in a Parkinson-like condition caused by protoxin MPTP injections in C57BL/6 mice. SkQ1 administration increased dopamine quantity and decreased signs of sensory-motor deficiency as well as destruction of dopaminergic neurons in the substantia nigra and ventral tegmental area in mice with the Parkinson-like condition.

The aim was to assess the efficacy of mitochondriatargeted antioxidant SkQ1 in prevention of structural and functional abnormalities of brain postresuscitation after cardiac arrest.Materials and methods. Adult male Wistar rats (n=19) underwent cardiac arrest for 7 minutes followed by resuscitation. Nine rats were administered with 500 nmol/kg SkQ1 per os with water for 2 weeks (1 week before and 1 week after resuscitation). A control group consisted of shamoperated animals (n=10). At days 4—6 post operation locomotor activity and anxiety («elevated plus maze» test) and sensorimotor function of limbs («beam walking» test) were examined. Total numbers of neurons per 1 mm of their layer length in vulnerable neuronal populations (cerebellar Purkinje cells and piramidal neurons of hippocampus fields CA1 and CA4) were estimated by histological analysis of the specimens stained with cresyl violet on day 7 postresuscitation. To identify possible mechanisms of SkQ1 action, the immunohistochemical study of a glialderived neurotrophic factor (GDNF) expression in piramidal neurons of hippocampus was performed by indirect peroxidaseantiperoxidase method and antiGDNF primary polyclonal antibodies.Results. Ischemiareperfusion resulted in neuronal loss in all studied brain areas followed by reduction in locomotor activity and development of sensorimotor deficit. SkQ1 prevented development of postresuscitative locomotor and sensorimotor irregularities, significantly reduced Purkinje cells loss, prevented death of piramidal neurons in hippocampal field CA4, but not in CA1. Data demonstrated, that iIn Purkinje cells from resuscitated rats treated with SkQ1 there was a significant increase in number of GDNFpositive neurons, which were more resistant to ischemia (transition of GDNFnegative cells toward the category of cells actively expressing this factor) that promoted their survival postresuscitation.Conclusion. Data confirm the positive effects of SkQ1 on structural and functional status of the brain postre suscitation and suggest possible use of SkQ1 for the prevention or correction of posthypoxic encephalopathies.

The aim was to assess the efficacy of mitochondriatargeted antioxidant SkQ1 in prevention of structural and functional abnormalities of brain postresuscitation after cardiac arrest. Materials and methods. Adult male Wistar rats (n=19) underwent cardiac arrest for 7 minutes followed by resuscitation. Nine rats were administered with 500 nmol/kg SkQ1 per os with water for 2 weeks (1 week before and 1 week after resuscitation). A control group consisted of shamoperated animals (n=10). At days 4—6 post operation locomotor activity and anxiety («elevated plus maze» test) and sensorimotor function of limbs («beam walking» test) were examined. Total numbers of neurons per 1 mm of their layer length in vulnerable neuronal populations (cerebellar Purkinje cells and piramidal neurons of hippocampus fields CA1 and CA4) were estimated by histological analysis of the specimens stained with cresyl violet on day 7 postresuscitation. To identify possible mechanisms of SkQ1 action, the immunohistochemical study of a glialderived neurotrophic factor (GDNF) expression in piramidal neurons of hippocampus was performed by indirect peroxidaseantiperoxidase method and antiGDNF primary polyclonal antibodies. Results . Ischemiareperfusion resulted in neuronal loss in all studied brain areas followed by reduction in locomotor activity and development of sensorimotor deficit. SkQ1 prevented development of postresuscitative locomotor and sensorimotor irregularities, significantly reduced Purkinje cells loss, prevented death of piramidal neurons in hippocampal field CA4, but not in CA1. Data demonstrated, that iIn Purkinje cells from resuscitated rats treated with SkQ1 there was a significant increase in number of GDNFpositive neurons, which were more resistant to ischemia (transition of GDNFnegative cells toward the category of cells actively expressing this factor) that promoted their survival postresuscitation. Conclusion. Data confirm the positive effects of SkQ1 on structural and functional status of the brain postre suscitation and suggest possible use of SkQ1 for the prevention or correction of posthypoxic encephalopathies.

Mitochondrial tRNA mutations are one of the important causes of both syndromic and non–syndromic deafness. Of those, syndromic deafness–associated tRNA mutations such as tRNALeu(UUR) 3243A>G are often present in heteroplasmy, while non–syndromic deafness–associated tRNA mutations including tRNASer(UCN) 7445A>G are often in homplasmy or in high levels of heteroplasmy. These tRNA mutations are the primary mutations leading to hearing loss. However, other tRNA mutations such as tRNAThr 15927G>A and tRNASer(UCN) 7444G>A may act in synergy with the primary mitochondrial DNA mutations, modulating the phenotypic manifestation of the primary mitochondrial DNA mutations. Theses tRNA mutations cause structural and functional alteration. A failure in tRNA metabolism caused by these tRNA mutations impaired mitochondrial translation and respiration, thereby causing mitochondr ial dysfunctions responsible for deafness. These data offer valuable information for the early diagnosis, management and treatment of maternally inherited deafness.

The influence of a course of medical treatment with the Semax nootropic peptide (50 and 200 mu g/kg) on alcohol motivation and general behavior was studied in rats preliminarily alcoholized over six months. Semax was also included in the scheme of complex therapy of human alcohol dependence in clinical practice. Experiments with rats showed an increase in the locomotor and exploratory activity of rats and a decrease in the degree of depressive-like components. This effect compensated the behavioral changes observed in the control group exposed to alcohol deprivation. At the same time, the behavior of test groups under anxiogenic conditions showed increased anxiety. Semax in a dose of 200 mu g/kg caused a significant increase in alcohol motivation, whereas its lower dose induced no proalcohol effect. Clinical trials demonstrated the safety (the absence of side effects and fairly high tolerance) of Semax in the course of alleviating the acute withdrawal syndrome and its efficacy for the recovery of mnestic functions (which was similar to the efficacy of Pyracetam). Semax did not change the frequency of cases of pathological craving for alcohol, but increased the overall intensity of behavioral reactions, which made the craving for alcohol stronger. These results allowed determination of safe course doses of Semax (to 50 mu g/kg) under conditions of chronic alcoholization and inclusion of this nootropic agent in a scheme of complex therapy for patients with alcohol dependence. The mechanisms underlying the individual differences in the effects of Semax should be studied further.

The study experimentally assessed the approach proposed by the authors to lower alcohol motivation, which involves enhancement of a specific immunity at the stage of alcoholization when acetaldehydemodified ethanol exchange enzymes [alcohol dehydrogenase (ADH)] and acetaldehyde dehydrogenase may be expected to occur. Omega-3 polyunsaturated fatty acid (PUFA) drugs enhance the formation of autoantibodies to modified ADH and decrease the activity of ADH in the stomach and liver. At the same time, PUFA drugs can, under certain conditions, produce an anti-alcoholic activity and a positive effect on the psychoemotional status of animals after the ethanol deprivation period.

We evaluated the effect of eiconol containing polyunsaturated fatty acids on the behavior and alcohol motivation in rats. Administration of eiconol for 10 days to alcoholized rats against the background of ethanol deprivation produced a sustained suppression of alcohol motivation and corrected deprivation-specific behavior.