Acute social isolation and regrouping cause short- and long-term molecular changes in the rat medial amygdala

Social isolation poses a severe mental and physiological burden on humans. Most animal models that investigate this effect are based on prolonged isolation, which does not mimic the milder conditions experienced by people in the real world. We show that in adult male rats, acute social isolation causes social memory loss. This memory loss is accompanied by significant changes in the expression of specific mRNAs and proteins in the medial amygdala, a brain structure that is crucial for social memory. These changes particularly involve the neurotrophic signaling and axon guidance pathways that are associated with neuronal network remodeling. Upon regrouping, memory returns, and most molecular changes are reversed within hours. However, the expression of some genes, especially those associated with neurodegenerative diseases remain modified for at least a day longer. These results suggest that acute social isolation and rapid resocialization, as experienced by millions during the COVID-19 pandemic, are sufficient to induce significant changes to neuronal networks, some of which may be pathological.