Long-Term Impacts of Post-weaning Social Isolation on Nucleus Accumbens Function

Abstract

Adolescence is a period of incredible change, especially within the brain's reward circuitry. Stress, including social isolation, during this time has profound effects on behaviors associated with reward and other neuropsychiatric disorders. Because the Nucleus Accumbens (NAc), is crucial to the integration of rewarding stimuli, the NAc is especially sensitive to disruptions by adolescent social isolation stress. This review highlights the long-term behavioral consequences of adolescent social isolation rearing on the NAc. It will discuss the cellular and molecular changes within the NAc that might underlie the long-term effects on behavior. When available sex-specific effects are discussed. Finally by mining publicly available data we identify, for the first time, key transcriptional profiles induced by adolescence social isolation in genes associated with dopamine receptor 1 and 2 medium spiny neurons and genes associated with cocaine self-administration. Together, this review provides a comprehensive discussion of the wide-ranging long-term impacts of adolescent social isolation on the dopaminergic system from molecules through behavior.

Post-weaning Social Isolation in Male and Female Prairie Voles: Impacts on Central and Peripheral Immune System

“…Moreover, it has been shown that neurochemical systems in the NAcc, such as CRF and OT, are critical for partner loss in prairie voles ( Bosch et al, 2016 ), and microglia can also directly interact with reward systems critical for pair bonding ( Loth and Donaldson, 2021 ). As the NAcc has been shown to be an important node for post-weaning-induced alterations ( Bendersky et al, 2021 ), we speculate that changes in microglia in the NAcc play a role in alterations to neuronal circuits and behaviors. Further, it has been reported that post-weaning isolation reduces the size of neurons and volume of the MeA ( Cooke et al, 2000 ), and microglia play a causal role in modulating underlying neurochemical alterations and behavioral outcomes from isolation stress ( Wang H. T. et al, 2017 ; Gong et al, 2018 ).…”

Prenatal Maternal Antibiotics Treatment Alters the Gut Microbiota and Immune Function of Post-Weaned Prepubescent Offspring

“…This is a critical time point in humans as a significant shift in the bacterial populations of gut microbiota occurs due to children switching to a solid and more varied diet; these and other age-related changes have huge implications on health [ 78 ]. In addition, in social isolation models of initiating neuropsychiatric disorders, the prepubescent period is a key time in behavior development [ 79 , 80 , 81 ]. The gut microbiota produces a large number of compounds that can influence health; most are beneficial [ 82 ], though others can be toxic, and changes in bacterial populations could potentially contribute to an increased risk of neurodevelopmental disorders.…”

Age-dependent effects of social isolation on mesolimbic dopamine release

“…The current study did not measure the duration of isolation-induced effects, but recent evidence suggests that social isolation and other stressful experiences during adolescence may result in long-term, even permanent changes in neural function (Bendersky et al 2021;Burke et al 2017). In the current study, the mice were isolated for 10-12 weeks, which is a relatively long isolation period, but it is possible that we could have seen more dopaminergic phenotypes develop had we tested later into adulthood.…”