Environmental enrichment prevents depression-like behaviours induced by immune system activation in male mice

Depression is a debilitating psychiatric illness, and its etiology as well as resistance to current pharmacological treatments are increasingly associated with low-grade inflammation. Environmental enrichment (EE), a paradigm that combines sensory and cognitive stimulation, social interaction, and voluntary physical activity, has been widely used to alleviate depression-like behaviours in rodent models, focusing on exposure to psychosocial stressors. However, the potential benefits of EE against depression-like behaviours triggered by immune activation remain unexplored. In this study, male C57BL/6 mice were housed under standard conditions or in EE. After six weeks, mice received an intraperitoneal injection of either physiological saline (vehicle) or lipopolysaccharide (LPS), a potent immunologic stimulus. Twenty-four hours later, anhedonia and behavioural despair were evaluated using the tail suspension test (i.e., frequency, latency, and time of immobility) and the splash test (i.e., latency, frequency, and time of grooming), respectively. LPS administration induced behavioural alterations consistent with depression-like behaviours characterised by increased immobility and decreased grooming. Remarkably, EE exposure prevented the development of LPS-induced depression-like behaviours in the tail suspension test and improved specific parameters in the splash test. Taken together, these findings highlight the therapeutic potential of EE as a non-pharmacological strategy for preventing or alleviating immune system activation-associated depression.