Effects of lipopolysaccharide administration and maternal deprivation on anxiety and depressive symptoms in male and female Wistar rats: Neurobehavioral and biochemical assessments

Abstract

Introduction: Preclinical studies of early-life adversity (ELA¹) have highlighted the role of postnatal stress in the emergence and persistence of anxiety and depressive disorders. In this study, we compared anxious and depressive behaviors and oxidation levels in male and female Wistar rats subjected to three ELAs (lipopolysaccharide (LPS) induced, maternal deprivation (MD), or combination of the two stressors).

Methods: Rats were split into four groups: control group which received an intraperitoneal (IP) injection of saline on postnatal day (PND) 1, LPS-treated group which received an IP injection of LPS on PND1, MD group which was exposed to a 24-hour period of isolation on PND9, and LPS-treated/MD group which received an IP injection of LPS on PND1 then was exposed to a 24-hour period of isolation on PND9. Each group consisted of 12 rats and had an equal gender distribution. At three months, rats were subjected to neurobehavioral assessments and biochemical oxidative assays.

Results: Compared to controls, rats in the LPS and MD groups scored significantly higher on anxiety and depression-related measures. Gender differences in response were mainly observed in the MD group. Exposure to the combination of stressors led to a characteristic decrease in anxiety and an increase in depressive measures in both genders. All groups exposed to ELA showed a statistically significant increase in their oxidative stress levels.

Conclusion: Response to ELA is gender-dependent and modulated by the nature, type, and number of stressors. Further investigations are critical to understand the mechanisms underlying combination of stressors and gender's effect.

Keywords: Anxiety; Depression; Early-life adversity; Lipopolysaccharide; Maternal deprivation; Oxidative stress.