Effects of Chronic Social Defeat Stress on Behavior and Dopamine Receptors in Adolescent Mice With 6-Hydroxydopamine Lesions of the Medial Prefrontal Cortex.

Tong Zhao,Guang-Biao Huang,Xiaolei Gao

doi:10.3389/fnbeh.2021.731373

Abstract

Background: Social stress factors in schizophrenia have long-term effects, but will only induce symptoms in a portion of individuals, even if exposed to identical stress.Methods: In the current experiment, we examined mice with 6-hydroxydopamine (6-OHDA)-induced medial prefrontal cortical (mPFC) injury to select for members of a “stress-susceptible group,” and observed the changes in their behavior and the expression of D1 and D2 dopamine receptors in the amygdala and hippocampus.Results: We observed that after chronic social defeat stress, 72.6% of the 6-OHDA lesioned mice exhibited stress response to aggressors, compared to 52.3% of the blank control group. Both the 6-OHDA lesion + social defeat and social defeat groups exhibited anxiety and depression-like behavior. However, social cognitive impairment in the mice from the 6-OHDA lesion + social defeat group was more significant and the D1 expression levels in the amygdala were significantly decreased.Conclusion: These results suggest that the reason that adolescent mice with cortical injury were highly sensitive to defeat stress and had more prominent social cognitive impairment may be the decreased selectivity of D1 in the amygdala.

Highlights

A large body of research has amassed suggesting that social defeat stress research may be able to explain the role of environmental factors in the pathogenesis of schizophrenia
The results showed that the protein expression of tyrosine hydroxylase was significantly decreased after the 6-OHDA microinjection compared with the control group [t = 3.055 p = 0.01] and the vehicle group [t = 2.943 p = 0.0123] (Figures 4A–D) but no significant changes in the protein expression of dopamine beta-hydroxylase were observed (Figures 4E–H)
After the chronic social defeat stress, 72.6% (n = 45) of the 6-OHDA lesioned mice, 52.3% (n = 34) of the socially defeated mice, and 53.7% (n = 32) of the mice that received vehicle while suffering social defeat exhibited stress responses when exposed to the aggressor

Summary

Introduction

A large body of research has amassed suggesting that social defeat stress research may be able to explain the role of environmental factors in the pathogenesis of schizophrenia. Social defeat stress and the aforementioned risk factors have similar face validity. Animal studies have reported an increased firing frequency of dopaminergic neurons in the ventral tegmental area, dopamine hypermetabolism in the marginal and cortical zones in the midbrain, and sensitization to amphetamines in social defeat animals (Tidey and Miczek, 1996; Yap et al, 2005; Cao et al, 2010; Razzoli et al, 2011). These results are similar to the pathophysiology of schizophrenia. Social stress factors in schizophrenia have long-term effects, but will only induce symptoms in a portion of individuals, even if exposed to identical stress

Methods

Results

Discussion

Conclusion