Uticaj oksitocina na aktivnost osovine hipotalamus-hipofiza-nadbubreg i ponašanje pacova

Abstract

Poremećaji raspoloženja, uključujući i depresiju, predstavljaju ozbiljne zdravstvene probleme i prema podacima Svetske zdravstvene organizacije do 2020. godine postaće vodeći uzrok radnog onesposobljavanja na globalnom nivou. Poznato je da je hiperaktivnost osovine hipotalamus-hipofiza-nadbubreg (HPA) čest pratilac depresivnih poremećaja, kao i da je hronična izloženost stresu vodeći faktor rizika u razvoju ovih bolesti. Jedan od najvećih problema farmakoterapije depresije predstavlja prilično veliki procenat neadekvatnog odgovora pacijenata na terapiju selektivnim inhibitorima preuzimanja serotonina (SSRI), koji predstavljaju lekove prvog izbora. Stoga, identifikacija biomarkera povoljnog odgovora na terapiju atnidepresivima, kao i pronalaženje eventualnog dodatnog tretmana koji bi povećao verovatnoću dobrog odgovora na terapiju od velikog je kliničkog značaja. Poslednjih godina pokazano je da hormon oksitocin učestvuje u modulaciji ponašanja i raspoloženja kao i da ima ulogu u adaptaciji organizma na hronični stres. Cilj istraživanja obuhvaćenih ovom doktorskom disertacijom bio je da se ispita uticaj oksitocina na ponašanje i parametre aktivnosti HPA osovine u modelu hroničnog stresa/depresije indukovane dugotrajnom primenom kortikosterona kod pacova Wistar soja. Takođe, cilj je bio i da se u navedenom modelu ispita efekat dodatnog tretmana oksitocinom uz antidepresiv citalopram, lek iz grupe SSRI. Da bi se realizovali postavljeni ciljevi, istraživanja su podeljena u tri faze. U prvoj fazi, ispitivan je uticaj različite dužine tretmana kao i različitih doza oksitocina na ponašanje i nivo biogenih amina u plazmi pacova. U drugoj eksperimentalnoj fazi, ispitivan je uticaj tretmana oksitocinom u dozi 10 IU/400 μL, s.c., tokom 14 dana na ponašanje i parametre aktivnosti HPA osovine u modelu hroničnog stresa/depresije izazvane primenom kortikosterona u dozi 100 mg/L, per os, tokom 21. dana...

Mood disorders, with depression leading the way, are severe health problems and according to the World Health Organization, depression is becoming the leading cause of disability worldwide. It is known that depressive disorders are frequently accompanied with hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis, as well as that the chronic stress is one of the most important risk-factors for its development. One of the most important problems of depressive disorders pharmacotherapy is that fairly large percentage of patients does not respond adequately to the therapy with selective serotonin reuptake inhibitors (SSRI), which are the first-line treatment drugs. Therefore, the identification of biomarkers of favorable response to antidepressant therapy, as well as discoveries of potential additional treatments, which would increase the probability of favorable response to the primary therapy is of the major clinical importance. In recent years, it has been shown that the hormone oxytocin modulates mood and behavior, and mediates adaptation feedback-response against chronic stress. The aim of the doctoral dissertation research was to evaluate the influence of oxytocin on the behavior and parameters of HPA axis activity, in the model of the long-term corticosterone administration-induced depression-like symptoms in adult male Wistar rats. Furthermore, the aim was to examine the potential beneficial effect of administering oxytocin alongside citalopram, an antidepressant from SSRI group, in this animal model. In order to fulfil these aims, the experimental work has been conducted in three phases. In the first phase, the effects of different treatment durations and dosages of oxytocin on behavior and plasma levels of biogenic amines were evaluated. In the second experimental phase, the effects of 14-day long oxytocin treatment (10 IU/400 μL, s.c.) on behavior and HPA axis activity in the model of chronic stress/depression induced by 21-day long corticosterone administration (100 mg/L, per os) were investigated...