Long-Term Behavioral Effects of Post-weaning Social Isolation in Males and Females

Abstract

Adolescence is a developmental period associated with vast neural and behavioral changes which are accompanied by altered sensitivity to stimuli, both stressful and rewarding. Perturbations, especially stressful stimuli, during this period have been shown to alter behavior in adulthood. Social isolation rearing is one such perturbation. This review highlights the long-term behavioral consequences of adolescent social isolation rearing in rodents with a specific focus on anxiety- and addiction-related behaviors. Sex-specific effects are discussed where data are available. We then consider changes in monoaminergic neurotransmission as one possible mechanism for the behavioral effects described. This research on both normative and perturbed adolescent development is crucial to understanding and treating the increased vulnerability to psychiatric disorders seen in humans during this life stage.

Adolescent Social Isolation Reprograms the Medial Amygdala: Transcriptome and Sex Differences in Reward

“…While numerous studies have shown that adolescent SI increases preference for drugs of abuse in males, much less is known about females (Walker et al, 2019). We used cocaine conditioned place preference (CPP; 7.5mg/kg) to determine if adolescent SI induces sex-specific effects on reward sensitivity in adulthood ( Figure 1G,H).…”

“…Adolescent SI has been used for decades to influence anxiety-and drugrelated responses, but very few studies have included females and most have not resocialized animals before testing. Since SI itself is stressful, not rehousing animals before testing makes it difficult to determine if its long-term effects are due to the stress of SI itself or if the adolescent period is a sensitive window for life-long effects (Walker et al, 2019). The present study is unique in its investigation of adolescence as a sensitive window for the development of sex-specific anxiety-and cocaine-associated behaviors in adulthood.…”

“…Adolescence is a sensitive period for programming reward-associated behaviors particularly in males (Sisk, 2016;Walker et al, 2019) and a time of heightened responsiveness to rewarding and stressful…”

“…Stressful and rewarding stimuli are two key factors that may be especially important for encoding these strategies to optimize sexual behaviors and maximize reproductive success . However, very little is known about the brain region-specific m o l e c u l a r p r o c e s s e s u n d e r l y i n g t h e programming of such strategies.Adolescence is a sensitive period for programming reward-associated behaviors particularly in males (Sisk, 2016;Walker et al, 2019) and a time of heightened responsiveness to rewarding and stressful…”

“…Recent evidence suggests that the adolescent period may be akin to other critical windows of development, such as sexual differentiation of the brain (Arnold, 2017) and experience-dependent plasticity of the visual system (Hensch, 2005). Stress during adolescence profoundly influences adult behaviors, with adolescent social isolation (SI) in particular altering anxiety-and reward-associated behaviors long-term (Walker et al, 2019): SI increases preference for numerous drugs of abuse including cocaine as well as anxiety-and depression-related behaviors in males (Lukkes et al, 2009;McCormick and Green, 2013;Walker et al, 2019). While decades of research have examined how adolescent SI programs male behavior, much less is known about females (Walker et al, 2019).…”