Gestational Stress and Oxytocin-Dopamine Interactions in New Mothers

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 DESCRIPTION (provided by applicant): Postpartum depression is a debilitating disorder affecting an estimated 20% of new mothers making it one of the most prevalent mental health conditions in women. In addition to classical depressive symptoms, postpartum depression is accompanied by disrupted caregiving which can have long-lasting deleterious effects on offspring development. The long-term goal of this project is to identify the key brain regions and neurochemicals acting in those regions that are responsible for impaired caregiving in depressed mothers in order to better understand the etiology of such impairments and how they can be effectively treated. To achieve that goal, animal models that incorporate known risk factors for postpartum depression provide a valuable translational tool. Epidemiological studies have shown that chronic stress during pregnancy is a major risk factor for postpartum depression. Like humans, pregnant rodents exposed to chronic gestational stress exhibit increased depressive-like behaviors during the postpartum period along with deficits in maternal behavior. Thus, the objective in this application is to use gestational stress to mechanistically study parenting deficits that are characteristic of postpartum depression. In this regard, maternal care is a rewarding, motivated behavior that like other types of motivated behaviors, involves the mesolimbic dopamine (DA) system, particularly DA projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) shell. An increasing number of studies suggest that oxytocin (OT) circuits from the paraventricular nucleus (PVN) and medial preoptic area (mPOA) of the hypothalamus closely interact with the DA system to regulate mother-infant interactions. The central hypothesis of this proposal is that gestational stress diminishes the motivation to engage in maternal care through a disruption in OT-DA interactions. We will use behavioral, neuroanatomical and neurochemical approaches to test our central hypothesis in two Specific Aims. Aim 1 will determine the extent to which the adverse effects of gestational stress on maternal motivation and maternal care are associated with altered DA activity in the postpartum NAc. Aim 2 will examine the effects of gestational stress on OT and OT inputs to the mesolimbic DA system. In these aims, targeted pharmacological manipulations of DA and OT will also be employed to examine the extent to which stress-induced deficits in maternal care and maternal motivation can be reversed. The proposed research is significant because it will provide much needed insight into the fundamental neurobiological mechanisms underlying impaired maternal functioning associated postpartum depression.