Infralimbic Cortex and Behavioral Responses to Mild Stress after Repeated Social Stress Exposure

Abstract

Major Depressive Disorder (MDD) is an emotional impairment that can have debilitating consequences for afflicted individuals. Social stress, including isolation or alienation, may be an important factor that contributes to MDD. In two experiments, repeated social defeat was utilized in rodents to induce social stress, modeling the social stressors that are thought to contribute to MDD in humans. Behavioral analyses revealed that dominance and submissive behaviors in the social defeat sessions were quite stable across repeated sessions. Accordingly, there appeared to be little variability between the rats in their social stress experience. This validates the model and allows for the study to draw inferences concerning the impacts of the stress experience from means testing of behavioral and physiological outcomes. The second experiment evaluated the impacts of repeated social defeat on cortical responses to the mild stress of a novel environment. RNAscope was utilized evaluate expression of c-Fos, GAD65, and VGluT1 mRNA in the infralimbic cortex. mRNA for c-Fos was labeled to identify which neurons were active in the infralimbic cortex. This was combined with labels for vGluT1 and GAD65 mRNAs to evaluate if those neurons were excitatory (glutamatergic) or inhibitory (GABAergic). The socially stressed rats exhibited increased mRNA expression for GAD65 in the infralimbic cortex. This suggests increased stress-induced biosynthesis of GABA in inhibitory neurons of the infralimbic cortex.