Nikanor V. Lavrov’s research while affiliated with Saint Petersburg State Pediatric Medical Academy and other places

An increase in the number of patients with psychodermatological manifestations and the identification of a certain comorbidity during the course of diseases in patients with a dermatological profile makes us take a fresh look at this problem. Psychodermatology is one of the relevant and, at the same time, the least studied areas of modern medicine, which is at the junction of psychiatry and dermatovenereology. Psychiatry and psychotherapy studies the inner world of a person; Dermatovenerology deals with the diagnosis and treatment of diseases of the human skin and its appendages, and psychodermatology combines these two sections of medicine. In the modern world, as a result of increasing the amount of incoming sensory information, accelerating the rhythm of life, the action of harmful environmental factors, a person can be subjected to excessive psycho-emotional stress, leading to the development of mental disorders. Often it is skin rashes that are an objective manifestation of such disorders. Early diagnosis of psychodermatosis and signs of obsessive-compulsive pathology in sick people contributes to the timely identification of the category of people at risk of psychotic reactions and mental illness. This is especially true for young patients. Against the background of hormonal changes in the body, the crisis of adolescence, the increased educational load on them at school, the destroyed institute of family and marriage, an overabundance of sensory information and physical inactivity, the incidence of psychodermatosis throughout the world, including in our country, is increasing.

The purpose of the review was to analyze the neurochemical and neurophysiological mechanisms of the ghrelin system and the role of ghrelin in body functions and behavior. The focus is on the participation of ghrelin in the mechanisms of reinforcement and the formation of addictive behavior. At the beginning of the review a history of the first works on the field of ghrelin and its receptor was described. Then, genetic control, molecular precursor of ghrelin, molecular forms of ghrelin and ghrelin receptor were represented. In particular, the distribution of the ghrelin receptor, ghrelin-producing cells in the brain and its participation in various physiological functions of the body were shown. The hypothalamic functions of ghrelin were discussed: energy balance, regulation of glucose metabolism, stimulation of eating behavior, regulation of hypophys-pituitary axis (HPA) system. The connection of ghrelin with the brain CRH system was demonstrated. In particular, activation of HPA was described as a possible mechanism through which ghrelin regulates a number of physiological processes. Extrahypothalamic action of ghrelin was shown on the basis of the mechanisms of reinforcement and addiction. On the basis of their own data and literary, it was concluded that action of alcohol and psychoactive drugs are reduced after the ghrelin receptors blockade. In particular, it has been demonstrated that alcoholization of mothers affects the activity of the ghrelin system during the prenatal and early postnatal periods of development in the offspring of rats. It was shown the participation of ghrelin in memory and learning. The further perspective of the study and practical application of ghrelin-based pharmacological agents was analyzed.

The purpose of the review was to analyze the neurochemical and neurophysiological mechanisms of the orexin system and the role of orexin in body functions and behavior. The focus is on the participation of orexin in the mechanisms of reinforcement and the formation of addictive behavior. At the beginning of the review a history of the first works on the field of orexin and its receptors are described. Hypothalamic orexin-producing cells and effects on brain functions are described. The effects of orexins and their receptors on eating behavior, wakefulness and positive reinforcement are described. Then, the effects of orexins on narcolepsy was analyzed. The participation of orexins in the mechanisms of reinforcement and dependence and the key role of orexins in the development of addictive behaviors is described. The special role of orexin in the formation of ethanol dependence is shown. Next, the issue of the action of orexins under stress was considered. Orexins have been shown to play an important role in the regulation of the nervous and humoral mechanisms mediating the formation of emotional memory associated with negative experience. It is concluded that orexin can modulate the estimation of stress and probability for reaching stimulus. In this regard, orexin antagonists can be considered as possible promising means of preventing and treating disorders of the anxiety-phobic spectrum, as well as disorders associated with the use of addictive drugs caused by stress and environmental stimuli.

The study of disorders of brain activity related to the violation of socialization is the current scientific problem. The article presents a review of the literature regarding the epidemiology, etiology and treatment of autism spectrum disorders. Special attention is paid to experimental models of autism, since simulation allows to test hypotheses about the nature of the disease and to carry out testing of new treatment methods. (For citation: Lavrov NV, Shabanov PD. Autism spectrum disorders: etiology, treatment. Models and experimental studies. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):21-27. doi: 10.17816/RCF16121-27).

The purpose of the paper was to study both the desacylghrelin (unacylated ghrelin) level in the blood serum and expression of mRNA ghrelin receptor in the brain structures in ontogeny after chronic alcoholization in rats. The results proved that the prenatal effect of ethanol negatively affected the maturation of dopaminergic and ghrelin systems of the brain as well as involvement of ghrelin system in mechanisms of alcohol dependence formation. The decrease of COMT mRNA expression simultaneoully with the increase of expression of D2 long and short isoforms of dopaminergic receptors and misbalance of ghrelin system were observed. Alcoholization of mothers reduced desacylghrelin level in the blood serum in early postnatal period in offsprings although mRNA expression of ghrelin receptor in the brain was elevated. Chronic alcoholization of adult rats also affected the ghrelin system. In the alcoholiztion process, the reduced contents of desacylghrelin in the blood serum with compensatory increase of ghrelin receptor expression in the brain were registered. After withdrawal of ethanol, the recovery of desacylghrelin level (tendency to normalization) was observed.

Ghrelin is a peptide hormone synthesized and secreted by the stomach into the bloodstream. The greatest attention of neuroscience research is devoted to investigation of acylated form of ghrelin, which is a specific ligand for the receptor subcortical nuclei of the brain. The aim of this study was to analyze the action of ghrelin and its antagonist on the expression of conditioned place preference (СPP) of ethanol. To develop CPP of alcohol we used a two-chamber apparatus. Rats were spent 74 % of time experiment in chamber associated with alcohol. Rats receiving intranasal receptor ghrelin antagonist [D-Lys3]-GHRP-6 (10 µg) reduced the time of staying in the chamber associated with alcohol for 46 % (p < 0.05). Rats treated with intranasal ghrelin spent in the chamber, associated with alcohol, for 60 % of time. Then the extinction of CPP was produced when rats was replaced into the apparatus every day for 7 days without administration alcohol or any substances. On the 7th day of extinction, CPP was not reproduced. But after administration of ethanol on the 7th day CPP was reinstated. Animals received GHS-R1A receptor ghrelin antagonist [D-Lys3]-GHRP-6 (10 µg) and ethanol spent 50 % of time in chamber associated with the administration of ethanol, i.e. CPP was not reinstated. Animals treated with ghrelin, demonstrated a range of reactions from a sharp preference to avoidance of the place associated with ethanol. Thus, the present study shows the important role of ghrelin in the mechanisms of the reinforcing effects of alcohol and demonstrates the prospect for using of ghrelin antagonists in the correction of pathological craving in addictive disordes.

The analysis of phychopharmacological profile of 9 peptide drugs (cortexin, cerebrolysine, deltaran, cortagen, oleyl-cortagen, semax, selank, noopept, dilept) in comparison with piracetam and mexidol was shown that cerebrolysine (1 mg/kg), oleyl-cortagen (1 mg/kg) and piracetam (200 mg/kg) possessed activating effect on motor and research components of behavior in «open field» test, and piracetam and cerebrolysine increased the emotional status of rats. Deprimating type of action was revealed in dilept (1 mg/kg), which decreased horizontal and vertical motor activity in rats. Only one peptide, selank (0.1 mg/kg), possessed antiaggresion action. A number of peptides (oleyl-cortagen, dilept and cortexin) demonstrated antidepressant effects, while cerebrolysine (1 mg/kg), oleyl-cortagen (1 mg/kg) and selank (0.1 mg/kg), on the other hand, performed depressant action on rat behavior in the Porsolt' test. Therefore, the significant psychoactivating properties are typical for cerebrolysine, oleyl-cortagen, cortexin and piracetam, while dilept, selank and in the less degree semax inhibited rat behavior, demonstrating deprimating type of action.

We compared central effects of polypeptide preparations cortexin and cerebrolysin injected into brain ventricles of Wistar rats in doses of 1, 10, and 100 microg. Both drugs exhibited moderate psychoactivating effect, the effects cortexin were more pronounced compared to those of cerebrolysin in all tests.

Young Wistar rats aged 4 days were injected intraperitoneally with corticotropin releasing hormone (CRH), which is an agent activating the stress system, or 70-kDa heat shock proteins (HSP-70)--intracellular shaperons, possessing antistress properties. In grown adult rats aged 90-100 days, the effects of nootropic drugs noopept and cortexin (1 mg/kg, i.p.) were assessed. The activation of stress or antistress systems with CRH or HSP-70 significantly altered the drug action. The effects were different in males and females and depended on animal gender. The spectrum of pharmacological activity of noopept and cortexin changed: noopept demonstrated preferable psychoactivating and antiaggressive effects, whereas cortexin showed mild anxiolytic and antidepressant activity. It is suggested that the behavioral effects of nootropes depend on the conditions of the stress system formation in early ontogeny.