STRESS-EVOKED MODELS COMBINATION IN THE RAT
László Ákos Kovács1, Anna Nafz1, Balázs Újvári1, József Farkas1, Tamás Gaszner1, Valér Csernus1, Balázs Gaszner1
Genetic, early-life and later environmental stress factors collectively may lead to manifest major depressive disorder (MDD). Besides the dysfunction of the hypothalamus-pituitary-adrenal axis including central corticortopin-releasing factor (CRF) the recruitment of the CRF-related peptide urocortin1 (Ucn1) and that of the serotonin (SER)-containing systems is also known in MDD. We hypothesized that the triple combination of factors results in depression-like behaviour with concomitant functional/morphological changes of central CRF, Ucn1 and SER systems in the rat. Wistar rats were categorized based on their low (LC), intermediate (IC) and high (HC) corticosterone response to acute stress. Litters of LC, IC and HC pairs were subjected to maternal deprivation (MD) vs. normal maternal care (NC). Half of the offspring was exposed later to chronic variable mild stress (CVMS) for 10 weeks. Behavioural assessment was performed by sucrose preference (SPT) and forced swim tests (FST). CRF, Ucn1 and SER systems were studied by multiple immunofluorescence labelling. Body, adrenal gland and thymus weights were measured to CVMS verification. LC-MD-CVMS animals showed the highest anhedonia in SPT. Depression-like behaviour in FST was the highest in the LC-NC-CVMS rats. The SERergic cell count in dorsal raphe nucleus (DR) was increased in the LC-MD-CVMS while HC-NC-CVMS animals showed low cell counts. No remarkable change was found in the CRF and Ucn1 systems. Our findings suggest that the history of MD affects DR-SER cells’ response to CVMS in offspring of LC rats and shapes mood-status. Supported by the ÚNKP-19-3-IV New National Excellence Program of the Ministry for Innovation and Technology.