A severe form of maternal separation in rat consisting of nineteen-day 6-hour daily separation at unpredictable times minimally affects behavior across the lifespan

Maternal separation (MS), a type of early life stress, has been associated with adverse socioemotional and behavioral outcomes throughout the lifespan across multiple species. Comprehensive longitudinal biobehavioral characterization of MS in rats is sparse and conflicting, warranting more studies. We conducted an MS paradigm involving 6-hour daily separation at unpredictable start times from P2 to P21. We hypothesized this severe form of MS would lead to developmentally emerging maladaptive biobehavioral consequences from juvenile through adult periods compared to Controls (C), especially in social behaviors. We tested: (1) own dam odor preference shortly after weaning; (2) juvenile and adult anxiety-like, sociability, and play behaviors using the light-dark test, three-chambered social interaction test, and video-coded juvenile play behavior; and (3) adult coping behaviors and neuroendocrine response using the forced swim test and blood corticosterone responses. Our results show minimal effects on biobehavioral outcomes across the lifespan. Recently weaned MS male rats had a stronger preference for their dam’s odor. Juvenile MS females spent more time in rough-and-tumble play than C female rats. No differences in sociability were found in the juvenile or adult periods. MS promoted a decrease in anxiety-like behavior that persisted from juvenile to adult periods. Finally, MS led to deficits in coping behavior in male adults, but basal and reactive corticosterone levels were unaltered by MS. More studies are needed to validate our surprising findings and probe the neural mechanisms underlying some of the observed protective effects. Significance Statement Maternal separation (MS), a type of early life stress, has been shown to lead to short and long-term adverse socioemotional consequences in humans and biobehavioral outcomes in rodents. Available data on MS exposed rats are sparse, conflicting, and often lack longitudinal outcomes. We designed a 6-hour unpredictable daily MS paradigm from postnatal day (P2) to P21 to severely disrupt normal dam-pup interactions. Our results show MS leads to increased preference for own dam odor, persisting reductions in anxiety-like behaviors from juvenile to adulthood, and no effects on sociability. Adverse effects on coping behaviors were uniquely identified in males. The present study warrants reevaluation of the central dogma that MS leads to maladaptive biobehavioral outcomes. ### Competing Interest Statement The authors have declared no competing interest.