Impact of early life adversity on caregiving behaviors and reward-related brain function: testing a mechanistic role for corticosterone

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PROJECT SUMMARY In both humans and rodents, parental care is disturbed by exposure to environmental adversity, including low resource conditions (i.e., poverty, scarcity). Maternal adversity is associated with compromised quality of mother- infant attachment and increased adverse caregiving patterns (i.e., maltreatment, neglect), which disrupt brain and behavioral development in the offspring. Importantly, maternal behavior is an intergenerational behavior, as the quality of maternal care a female experiences influences the quality of care she will give her own offspring. Indeed, clinical and preclinical research converge in showing that females with a history of early life adversity within the context of the caregiver (i.e., abuse, maltreatment) mistreat their own offspring. However, the neural changes associated with early life adversity-induced maladaptive maternal behavioral states remain poorly understood. One potential pathway is the mesolimbic dopamine (DA) system, which originates in the ventral tegmental area (VTA), is sensitive to early life stress, and is critically involved in reward-related processes- including maternal behavior. Moreover, the functional integrity of the VTA and mesolimbic DA signaling play a causal role in the adequate expression of maternal behavior. Thus, compromised activity of VTA DA neurons induced by early adversity may interfere with reward-related processes necessary for maternal motivation and responsiveness. However, little is known about the regulation of DA system function and its relation to caregiving behaviors in postpartum rodents following early life adversity. To this end, I employed a well-characterized manipulation based on creating an impoverished nesting environment during postpartum days (PD) 2-9 by providing the rat dam with limited bedding and nesting (LBN) materials, which increases stress hormone (i.e., corticosterone- CORT) levels in the dam and pups and disrupts mother-infant interactions, thereby mimicking the effects of a stressful environment in potentiating maltreatment/neglect in humans. I found increased negative maternal behaviors directed at pups, impaired motivated maternal responses and blunted VTA DA neuron activity at PD 9-10 in LBN-exposed dams. The overall goal of this proposal is to replicate my postdoctoral findings of postpartum adversity (LBN) effects on maternal behavior and mesolimbic DA function in the dam (in my independent lab) and extend them into an intergenerational examination of maternal behavior and mesolimbic DA function in the adult female offspring, while testing a mechanistic role for pup increases in CORT. The overarching hypothesis is that early life scarcity-adversity (LBN dam, PD 2-9) will induce impaired maternal behavior/disrupted mother-infant interactions and mesolimbic DA downregulation (i.e., VTA hypoactivity) in the adult female offspring in a CORT-dependent manner. I will test a mechanistic role for CORT by preventing the atypical infant increase in pup CORT levels and assessing whether it can circumvent early adversity effects on maternal behaviors and postpartum DA function in female offspring. In this way, I hope to provide insights into dopaminergic mechanisms contributing to early-adversity induced changes in mother-infant attachment.