The dissertation work is devoted to the study of the pathogenetic mechanisms of the depressive syndrome in the conditions of chronic convulsive syndrome and the development of a method of pathogenetically justified correction of depressive elements of behavior on this basis.The work solves the following tasks: to investigate changes in late tonic, swimming, emotional behavior, as well as mnestic functions in animals at the stages of developed pharmacological kindling, completed kindling and postkindling; to determine the effect of modulation of the cholinergic, dopaminergic and GABAergic systems of the striatum on the severity of the investigated types of behavior in rats in the dynamics of chronic convulsive syndrome; to determine the influence of modulation of cholinergic and opiatergic neurotransmitter systems and the system of excitatory amino acids in rats with kindling-induced chronic convulsive activity; to determine the effectiveness of separate and simultaneous administration of vortioxetine with valproic acid, diphenigdidantoin and phenobarbital in the aspect of recovery of detected behavioral disorders in rats in the dynamics of chronic convulsive syndrome; determine the effectiveness of separate and simultaneous administration of vortioxetine with anticonvulsant drugs in patients with post-traumatic epilepsy; based on the available experimental and clinical data, to substantiate the expediency of the combined use of anticonvulsant drugs and antidepressants under the conditions of complex pathogenetic therapy of depressive behavioral disorders. The dissertation research was carried out during 2016-2020. at the Department of General and Clinical Pathological Physiology of Odesa National Medical University. The research was carried out in several stages. The task of the first stage was to clarify the features and determine the dependence on the stage of formation of kindling-induced chronic convulsive activity of various forms of non-convulsive behavior of experimental animals. The task of the second stage of own research was to determine the effectiveness of correction of non-convulsive forms of behavior selected for research in rats at various stages of the formation of kindling-induced chronic convulsive activity. For this purpose, ready-made preparations registered in Ukraine, vortioxetine, valproic acid, diphenylhydantoin, and phenobarbital were used. The task of the third stage of own research was the clinical evaluation of the effectiveness of the scheme of pathogenetically justified pharmacological correction of non-convulsive varieties of behavior in patients with post-traumatic epilepsy. A model of chemical kindling was used to reproduce chronic convulsive syndrome. Different time intervals of the formation of chronic convulsive activity were used: the 18th day of kindling reproduction, which was considered the stage of a developed chronic convulsive syndrome, the 24th day of kindling reproduction, which is the stage of a formed chronic convulsive syndrome, and the postkindling stage (after a 14-day interval after the end of formation of kindling, 38 days of the experiment), which was considered a stage of increased convulsive readiness. The behavior of the animals was studied in periods of time free from convulsive manifestations - during interictal periods. The understanding of the pathophysiological mechanisms of the formation of non-convulsive forms of depressive behavior in the dynamics of kindling-induced chronic convulsive activity was supplemented, and the theoretical basis for the combined use of antidepressants and anticonvulsants in order to restore non-convulsive types of depressive-oriented behavior in chronic epileptization of the brain was developed. The chosen complex scheme of pharmacocorrection is effective, has a pathogenetic background and a pronounced sanogenetic influence, which in the case of further thorough research will have the prospect of clinical implementation in a significant contingent of epilepsy patients with comorbid depressive manifestations. Thus, the dissertation presents a theoretical generalization and a practical solution to an actual scientific problem: the study of the pathogenetic mechanisms of the depressive syndrome in the conditions of the chronic convulsive syndrome and, on this basis, the development of a method of pathogenetically justified correction of depressive elements of behavior.
