期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：3
页码：881-886
DOI：10.1073/pnas.1416065112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceInfant trauma induces preference learning about trauma-linked cues but negatively programs neurobehavioral development. Despite clinical evidence that trauma-linked cues remain powerful throughout life, the mechanisms underlying the interaction between infant trauma cues and the long-term effects of trauma are unknown. Using a rodent model of trauma bonding, which produces a life-long preferred odor and enduring effects that parallel the sequelae of child abuse, we show that the infant trauma odor rescues adult depressive-like behavior and amygdala dysfunction. Assessment of neural mechanism implicates amygdala serotonin (5-HT) and glucocorticoids (GCs). Our findings suggest that trauma-linked cues have an unexpected positive value in adulthood (i.e., antidepressant properties) and may provide insight as to why victims of childhood abuse are attracted to abuse-related cues. Children form a strong attachment to their caregiver--even when that caretaker is abusive. Paradoxically, despite the trauma experienced within this relationship, the child develops a preference for trauma-linked cues--a phenomenon known as trauma bonding. Although infant trauma compromises neurobehavioral development, the mechanisms underlying the interaction between infant trauma bonding (i.e., learned preference for trauma cues) and the long-term effects of trauma (i.e., depressive-like behavior, amygdala dysfunction) are unknown. We modeled infant trauma bonding by using odor-shock conditioning in rat pups, which engages the attachment system and produces a life-long preference for the odor that was paired with shock. In adulthood, this trauma-linked odor rescues depressive-like behavior and amygdala dysfunction, reduces corticosterone (CORT) levels, and exerts repair-related changes at the molecular level. Amygdala microarray after rescue implicates serotonin (5-HT) and glucocorticoids (GCs), and a causal role was verified through microinfusions. Blocking amygdala 5-HT eliminates the rescue effect; increasing amygdala 5-HT and blocking systemic CORT mimics it. Our findings suggest that infant trauma cues share properties with antidepressants and safety signals and provide insight into mechanisms by which infant trauma memories remain powerful throughout life.
