Resilience and vulnerability to stress-induced anhedonia differently affects the molecular acute responsiveness in the rat brain

Major depressive disorder (MDD) is a psychiatric disease characterized by low mood and anhedonia Although its etiology is associated with the interaction between vulnerability genes and environmental risk factors such as stress, it is important to note that not all stressed subjects develop the disease indeed some of them show resilience. The aim of this study was to evaluate if and how the vulnerability or resilience to the anhedonic phenotype induced in the rat by the chronic mild stress paradigm (CMS) could influence the molecular response to an acute challenge. In particular, we focused our attention on the redox system, which is altered in psychiatric diseases and is often acutely activated. Adult male Wistar rats were subjected to 3 weeks of CMS, divided in vulnerable and resilient groups based on their sucrose intake and then exposed again to 3 weeks of CMS. After that, half of these rats were subjected to an acute challenge by 1-hour restraint (ARS) at the end of which all animals were euthanized and the brain areas dissected for the subsequent gene expression analyses through qRT-PCR. We found a significant increase of the mRNA levels of several antioxidant genes (i.e. MT1a and SRXN1) after ARS, an effect observed only in CMS-vulnerable animals, Conversely, other genes such as CAT or GPX are less affected. Our results suggest that despite the “static” molecular impairment of the redox machinery induced by CMS, the behavioral consequences of the chronic procedure clearly influence the subsequent dynamic ability of the animals to respond to a second stimulus. In particular, we observed an increase in the antioxidant component in vulnerable rats and a decrease in resilient ones, a profile that might mirror a stronger need of the former to balance an oxidative state, that conversely is not necessary for the latter.