AGGRESSIVE BEHAVIOR CORRECTION BY THE TRANSPLANTATION OF IN VITRO MODULATED IMMUNE CELLS

Abstract

Aggression is a serious biomedical problem associated with a high percentage of patients and a lack of selective corrective agents. The most frequent increase in aggressiveness occurs in patients with depressive disorders, schizophrenia, reactive psychoses and adjustment disorders, which are known to be characterized by immunological dysfunction. Antipsychotics are widely used in the correction of psychomotor agitation; the antipsychotic effect of these drugs is manifested in the achievement of a sedative effect. However, like other psychoactive substances, they have a number of side effects that limit their long-term use and determines the need to search for new approaches to the correction of affective disorders. Experimental modeling of aggression is one of the main approaches for studying its pathogenetic mechanisms and searching for new effective therapeutic agents for the treatment. The study of the aggression pathogenetic mechanisms and the search for approaches to therapy within the framework of neuroimmune interaction is currently extremely promising. Currently, there is a large number of clinical and experimental data indicating interrelated changes in the functional activity of the nervous and immune systems during aggression. The leading links in the pathogenetic mechanism of aggression is the violation of the production and mutual regulation of cytokines, neurotransmitters, neuropeptides, growth factors, hormones, the effects of which are mediated by the cellular elements of the immune system. Given the immune cells essential role in the pathogenesis of aggression and the psychoactive substances unidirectional effect on the immune and nervous cells, make it possible to consider immune cells as model objects for influencing the intersystem functional relationship in order to edit the aggressive phenotype. The aim of the study was to investigate the effect of in vitro neuroleptic-modulated immune cells transplantation on behavioral phenotype and brain cytokines in aggressive syngeneic recipients. Aggressive behavior was formed in active male mice (CBA × C57Bl/6) F1 as a result of the experience of 20- fold victories in inter-male confrontations (distant sensory contact model). Aggressive mice splenocytes were treated in vitro with chlorpromazine and intravenously injected to syngeneic aggressive recipients. It has been demonstrated that modulated in vitro by chlorpromazine splenocytes of aggressive mice after transplantation edit the syngeneic aggressive recipient’s behavior against the background of a decrease in cytokines IL-1β, IL-2, IL-6, IFNγ and an increase in IL-4 in pathogenetically significant for aggression brain structures. The mechanisms of the aggressive behavior correcting effect of modulated immune cells are discussed.

Keywords

• aggressive behavior
• immune cells
• chlorpromazine
• brain structures
• cytokines