Reorganization of Brain Networks as a Substrate of Resilience: An Analysis of Cytochrome c Oxidase Activity in Rats

•The UCMS protocol induce anhedonic responses and elevated anxiety responses.•Environmental enrichment protocols induce resilience and brain reorganization.•Habenula hyperactivity may be an index of vulnerability to depressive disorders. The unpredictable chronic mild stress (UCMS) model has been used to induce depressive-like symptoms in animal models, showing adequate predictive validity. Our work aims to evaluate the effects of environmental enrichment (EE) on resilience in this experimental model of depression. We also aim to assess changes in brain connectivity using cytochrome c oxidase histochemistry in cerebral regions related to cognitive-affective processes associated with depressive disorder: dorsal hippocampus, prefrontal cortex, amygdala, accumbens, and habenula nuclei. Five groups of rats were used: UCMS, EE, EE + UCMS (enrichment + stress), BG (basal level of brain activity), and CONT (behavioral tests only). We assessed the hedonic responses elicited by sucrose solution using a consumption test; the anxiety level was evaluated using the elevated zero maze test, and the unconditioned fear responses were assessed by the cat odor test. The behavioral results showed that the UCMS protocol induces elevated anhedonia and anxiety. But these responses are attenuated previous exposure to EE. Regarding brain activity, the UCMS group showed greater activity in the habenula compared to the EE + UCMS group. EE induced a functional reorganization of brain activity. The EE + UCMS and UCMS groups showed different patterns of connections between brain regions. Our results showed that EE favors greater resilience and could reduce vulnerability to disorders such as depression and anxiety, modifying metabolic brain activity.