Behavior and oxidative stress parameters in rats subjected to the animal's models induced by chronic mild stress and 6-hydroxydopamine

Abstract

Major depressive disorder (MDD) is one of the most prevalent forms of mental illness also affecting older adults. Recent evidence suggests a relationship between MDD and neurodegenerative diseases, including Parkinson's disease (PD). Individuals with PD have a predisposition to developing MDD, and both neurobiological conditions are associated with oxidative stress. Thus, we conducted this study to investigate depressive-like behavior and oxidative stress parameters using both animal models of PD and stress. Adult Wistar rats were subjected to chronic mild stress (CMS) protocol by 40 days and then it was used 6-hydroxydopamine (6-OHDA) as a model of PD, into the striatum. The experimental groups were: Control + Sham, Stress + Sham, Control+6-OHDA, and Stress+6-OHDA. Depressive like-behavior was evaluated by the forced swimming test (FST) and spontaneous locomotor activity by open-field test. Oxidative stress parameters were measured in the striatum, hippocampus, and prefrontal cortex (PFC). The results showed effects to increase immobility and decrease climbing times in the FST in Stress + Sham, Control+6-OHDA, and Stress+6-OHDA groups. The number of crossings and rearings were decreased in the Stress+6-OHDA group. The lipid peroxidation was increased in the PFC of Stress + Sham, and the hippocampus and striatum of Stress + Sham and Control+6-OHDA groups. Carbonyl protein levels increased in the PFC of Stress + Sham and striatum in Control+6-OHDA. Nitrite/Nitrate concentration was elevated in the PFC of Stress + Sham, in the hippocampus of Control+6-OHDA, the striatum of Stress + Sham, and Control+6-OHDA groups. Myeloperoxidase (MPO) activity was increased in the PFC and hippocampus of Stress + Sham and Control+6-OHDA groups. The activity of catalase decreased in the PFC of the Stress + Sham group. The activity of the superoxide dismutase (SOD) was decreased in the PFC of the Stress + Sham group, in the hippocampus of Stress + Sham and Control+6-OHDA groups, and the striatum of Control+6-OHDA group. These findings suggest that both stress and 6-OHDA induce depressive-like behavior and oxidative stress in the brain. The joining models have little evidence of the effects. Thus these findings suggest that other pathways are involved in the common point of the pathophysiology of PD and MDD.

Keywords: 6-hydroxydopamine; Chronic mild stress; Major depressive disorder; Oxidative stress; Parkinson’s disease.