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.
