Effects of social isolation and loneliness during early life on neurocognitive development and addiction

Project Summary Social isolation (SI) and loneliness are associated with adverse health outcomes and are serious public health risks throughout life. In early life, SI has well known deleterious effects on socioemotional and cognitive development, and on the developing brain. SI and loneliness also can increase drug and alcohol usage in

adolescent humans and post-weaning SI increases cocaine and methamphetamine self-administration in rats. The mechanism by which SI impacts cognition and addictive behavior are mostly unknown, but they may involve disturbed sleep and neuroinflammation. Disturbed sleep has been suggested to be important in the

adverse effects of SI and loneliness, and sleep disturbances and the risk for SI and loneliness are common in adolescence. SI and loneliness can increase sleep disturbances and disturbed sleep negatively impacts cognitive performance. Disturbed sleep also heightens risks for substance use disorders (SUDs). SI can alter

microglia activity, which determines neuroinflammation levels. However, there have been few studies of how early SI, and degrees of isolation, impact cognition and addictive behavior. There also is minimal information as to the role disturbed sleep and neuroinflammation play in SI-induced changes in cognition and addictive

behavior in adolescence and potential persistence into adulthood. We will employ a paradigm comparing rats single-housed in standard transparent cages (SI) and rats single-housed with opaque barriers between cages to prevent visual contact (ESI, enhanced SI) to pair housed (PH) rats. In adult rats, chronic ESI, a putative

model of loneliness compared to SI alone reduced sleep, reduced EEG delta, produced different levels of neuroinflammation, and altered astrocyte morphology. There also were significant sex differences in sleep and behavior. We will use this model in our planning project to develop methods to assess the effects of SI and ESI

during development on neurocognitive function and addictive behavior in rats. We have assembled a multidisciplinary team with expertise in translational SUD research/addiction, neurocognitive testing, neural signal processing, sleep neurobiology, neurohistology and circadian rhythms to determine how SI and ESI

impact drug seeking and consummatory behavior, cognition and neurocircuit activity and the role that sleep may play in altered cognition and addictive behavior. We will develop methods and paradigms to assess, in adolescent and adult male and female rats, the effects of early life SI and ESI compared to PH on cognitive

performance and drug self-administration. We will also develop methods to record neural activity during cognitive testing and to assess sleep and neuroimmune function as mediators of SI- and ESI-induced effects. Our goal is to identify, and develop methods to pursue, promising lines of research that will increase

understanding of the effects of early life SI and loneliness on subsequent cognition and addictive behavior.