Graduation Date

Summer 8-14-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Ming Li

Abstract

Early life stress can induce persistent brain and behavioral alterations. As a lifetime history of clinical symptoms similar to those caused by early adversities may predict postpartum dysfunctions, these stressors likely contribute to their etiology. Postpartum neuropsychiatric disorders (e.g. postpartum depression, anxiety and depression) are costly, yet due to the complex neuronal reorganization during this period, insights into how early adversities-induced CNS functional changes affect postpartum processes remain limited, especially under multiple stressors. Thus, there is a need to determine postpartum functions altered by early stress, in order to increase understandings of risks associated with postpartum maladaptations. Accordingly, this work was designed to assess early stress-induced behavioral and neuronal changes in postpartum female rats, using pre- and postnatal stressors independently and concurrently. We hypothesized that pre- and/or postnatal insults would disrupt postpartum cognitive and affective regulations, maternal behaviors, and neuronal functions. Females exposed to maternal immune activation (MIA) in utero and/or repeated maternal separation (RMS) in the early postnatal period were assessed for maternal performance in postpartum. Prepulse inhibition (PPI) of acoustic startle response (ASR), forced swim test (FST), sucrose preference, fear potentiated startle (FPS), and conditioned avoidance response (CAR) were also tested in both dams and virgin littermates to assess various psychological functions. In neuronal functions, c-Fos expression following FPS, and amphetamine-, phencyclidine- (PCP), nicotine-, and 2,5-dimethoxy-4-iodoamphetamine-induced hyperlocomotion were examined. Results show that MIA reduced nest building in mother rats, as well as their PPI and CAR performance. MIA also increased dorsal medial preoptic area and dorsal periaqueductal grey c-Fos following FPS. In addition, virgin offspring exposed to MIA also showed reduced struggling behavior in the FST and increased basolateral and medial amygdala c-Fos following FPS. RMS reduced nest building, ASR, FPS, and amphetamine- and PCP-induced hyperlocomotion, and increased dentate gyrus c-Fos following FPS. MIA and RMS were antagonistic in maternal behaviors and ASR, and otherwise showed little interactive effects. Overall, these results indicate that early environmental stressors could have long-term impacts on postpartum functions, including maternal behavior and performances in various behavioral tests. This impact is also influenced by reproductive experiences.

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