Renin inhibitor attenuates lipopolysaccharide-induced anhedonia and upregulation of neuroinflammatory markers in mice

Evidence suggests that the inhibition of renin-angiotensin system can greatly decrease the neuroinflammation response. Neuroinflammation plays a pivotal role in the pathogenesis of depression characterized by the inability to experience pleasure in some patients. The aim of this study was to investigate the effects of aliskiren, a renin inhibitor, on lipopolysaccharide (LPS)-induced anhedonia and upregulation of neuroinflammatory markers in mice. Adult healthy male albino mice were divided onto two groups (control vs LPS). Animals in control group received saline, whereas animals in LPS group received 0.5 mg/kg of systemic LPS injection. Pretreatment of aliskiren was done in all groups at different doses (1, 3, and 10 mg/kg). Sucrose preference test (SPT) and open field test (OFT) were used for the assessment of anhedonia and locomotor activity respectively in mice. Proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and glial cells markers (CD11b for microglia and GFAP for astrocytes) in the prefrontal cortex were determined via RT-PCR. Results depicts that LPS was able to induce anhedonia and upregulate mRNAs of proinflammatory cytokines and glial cells markers after 24 h. Prophylactic treatment with aliskiren (10 mg/kg) significantly prevented LPS effects by increasing the consumption of sucrose in SPT. Locomotor activity in OFT did not show significant changes in aliskiren-pretreated mice 24 h after LPS administration. Aliskiren (10 mg/kg) significantly reduce LPS-induced upregulation of proinflammatory cytokines and glial cells markers in the prefrontal cortex. Taken together, the renin inhibitor aliskiren exerted beneficial effects in animal inflammation-based model of depression characterized by appearance of anhedonia and upregulation of neuroinflammatory markers.