The Benjamin Nephew Lab

Research Publications Neuroscience

 

A Chronic Social Stress Model for Postpartum Mood Disorders

One of the strongest predictors for depression and anxiety disorders in females is exposure to chronic social stress. Although depression is twice as likely in females than in males, the vast majority of depression research involves only male subjects. Postpartum depression and anxiety have negative effects on the health of both mother and offspring through effects on maternal behavior, yet little is known about the etiology of these disorders. The main focus of our lab is the development and investigation of an ethologically relevant rodent model for behavioral disorders in female maternal mammals, including depression and anxiety.

Nephew Fig 1

Figure 1. Exposure to chronic social stress starting on day 2 of lactation depresses maternal care on day 9 of lactation.

This area of study includes the neuroendocrine initiation and control of maternal behavior and the effects of stress on behavior, neuroendocrinology, and physiology in maternal females as well as transgenerational effects on male and female offspring.

 Nephew Fig 2

Figure 2. Exposure to early life chronic social stress (the F1 offspring of the maternal rats in Fig1) depresses maternal care on day 2 of lactation.

We have recently published reports on the effectiveness of a chronic social stress model that has substantial effects on the behavior, endocrinology, physiology, and neural activity of maternal rats and their offspring. These effects are similar to several postpartum mood disorder symptoms. Two key features of our model are the focus on maternal care to assess anhedonia and the investigation of effects on lactation, which is often disrupted in depressed and anxious mothers. Current endocrine and neural targets include oxytocin, vasopressin, estrogen, prolactin, and corticosterone.

Oxytocin, Postpartum Depression, Anxiety, and Autism

Central oxytocin activity is a potent modulator of social behavior, and disruptions in oxytocin have been linked to depression, anxiety, and autism. Exposure of lactating rats to chronic social stress, an ethologically relevant model for postpartum depression, induces alterations in central oxytocin receptor expression in the adult offspring which are associated with differential methylation of the oxytocin receptor promoter and effects on social behavior. The goal of this Tufts Clinical and Translational Science Institute funded project is to investigate the behavioral, genetic, and epigenetic effects of chronic social stress on depression, anxiety, and autism associated changes in maternal behavior and social behavior in males and females. It is hypothesized that chronic social stress will impair social behaviors in males and females and/or induce effects common to depression and anxiety and that these effects will be associated with epigenetically mediated changes in central oxytocin activity. Initial results indicate that female social play behavior is attenuated in the offspring of social stressed dams.

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Figure 3. Early life chronic social stress attenuates oxytocin gene expression in the hypothalmus and amygdala.

Data collected from this project will promote the increased use of ethologically designed behavioral models in the study of depression, anxiety, and autism and generate new insights into the etiology, prevention, and treatment of depression, anxiety and autism spectrum disorders through an interdisciplinary approach.

Cocaine, Maternal Behavior and Depression

I also collaborate with the lab of Dr. Marcelo Febo at the University of Florida in the study of the effects of cocaine on maternal behavior. Our projects focus on the use of neuroimaging to study the neural correlates of addiction and maternal behavior in rodent models. Functional magnetic resonance imaging (fMRI) allows us to noninvasively inspect in vivo brain activation in response to a variety of cognitive, emotional and drug stimuli.

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Figure 4. Previous adult sensitization to cocaine accelerates the development maternal care and increases neural activity in the anterior thalamus and periaqueductal gray in nulliparous rats.

The strength of the technique lies in the ability to conduct longitudinal functional studies in the same animal over its adult life. The relatively good spatial and temporal resolution and the ever-growing database on the biological and biophysical basis of the blood oxygen level dependent (BOLD) signal make it a unique technique in preclinical and translational neuroscience research. Recent studies from our labs have reported long term effects of prior cocaine exposure on maternal care and associated changes neural activity as well as identified the neural substrates of the effects of vasopressin on maternal aggression. We are currently investigating several areas of interest that include: (i) the long term impact of chronic cocaine exposure on the brain dopaminergic system, (ii) the role of brain oxytocin and vasopressin systems on the processing of social stimuli, and (iii) the specific roles of the medial prefrontal cortex on motivation and emotion. Our work will contribute significantly to understanding conditions such as postpartum depression and anxiety in addicted or recovering mothers.

Application for 2015 Admission

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