Abstract
Depression is a major psychological disorder that contributes to global health problem. This study aimed to evaluate the anti-depressant effect of Cerebrolysin (CBL) in Reserpine-induced depressed rats, its effect on oxidative stress, inflammation, regulatory cyclic AMP-dependent response element binding protein (CREB)/brain derived neumtropic factor (BDNF) signaling pathways, brain monoamines and histopathological changes was assessed. Rats received either the vehicle or Reserpine (0.5 mg/kg, i.p.) for 14 days. The other three groups were pretreated with CBL (2.5, 5 ml/kg; i.p.) or fluoxetine (FLU) (5 mg/kg, p.o.), respectively for 14 days, 30 min before reserpine injection. Then analyses were conducted. CBL reversed Reserpine-induced reduction in latency to immobility and prolongation of immobility time in the forced swimming test (FST), reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced tumor necrosis factor-alpha (TNF-alpha), and elevated BDNF cortical and hippocampal brain contents. CBL elevated protein kinase A (PKA) and nuclear factor kappa-B (NF-kappa B) cortical and hippocampal protein expressions. CBL also ameliorated alterations in mRNA expressions of protein kinase B (AKT), CREB and BDNF in the cortical and hippocampal tissues. CBL elevated nor-epinephrine (NE), semtonin (5-HT), and dopamine (DA) and reduced 5-Hydroxyindoleacetic acid (5-HTAA), 3,4-Dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) cortical and hippocampal contents. CBL effects were in parallel to those observed with the standard anti-depressant drug, FLU. This study shows that CBL exerted antidepressant effect evidenced by attenuation of oxidative stress and inflammation as well as enhancement of neurogenesis, amelioration of monoaminergic system and histopathological changes.