Early life stress is associated with various complications. Auraptene has significant antioxidant and anti-inflammatory effects. This study aimed to assess the probable underlying mechanisms that mediate changes in the behavior, hippocampus, heart and serum in the mouse model of maternal separation (MS) stress. We evaluated the possible protective effects of auraptene in these changes focusing on inflammatory response and oxidative state. Mice were treated with auraptene (5, 10, and 50 mg/kg). In addition, anxiety-like behaviors were evaluated using behavioral tests; including open field test (OFT) and elevated plus maze (EPM). Hippocampus and heart samples were assessed histopathologically. Levels of malondialdehyde (MDA) and antioxidant capacity, as well as nitrite levels, were measured in serum, heart, and hippocampal tissues. Moreover, gene expression of inflammatory markers (Il-1β and Tlr-4) was evaluated in the heart and hippocampus. Results showed that auraptene reversed the negative effects of MS on behavior (increased time spent in central zone of the OFT and time and entries to the open arms of the EPM). Auraptene mitigated adverse effects of MS on the hippocampus (increased diameter and decreased percentage of dark neurons in the CA3 area). Accordingly, auraptene decreased MDA and nitrite levels and increased the antioxidant capacity in serum, and hippocampal samples. However, we observed different effects for different doses of auraptene in the heart samples. We concluded that MS is associated with anxiety-like behavior and cellular/molecular modifications in the heart, hippocampus and serum. We found that auraptene exerted protective effects against these negative effects of MS in mouse.
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