High maternal anxiety has tremendously detrimental effects on maternal motivation, mother-infant interactions, and infant development. Although a large number of women experience elevated anxiety after giving birth, the neurobiological events responsible for high postpartum anxiety or its alleviation are very poorly understood. Physical contact with infants can reduce anxiety in postpartum women and other mammals, and is vital for healthy maternal emotional states. I propose to investigate the neural basis of how contact with infants modulates maternal neurochemistry to reduce anxiety. I am specifically interested in the involvement of the ventral bed nucleus of the stria terminalis (vBST) and three of its primary targets (central amygdala, supramammillary nucleus, and periaqueductal gray), which are all traditional components of the neural network regulating anxiety. The vBST has one of the densest noradrenergic innervations of the forebrain, and high noradrenergic tone in the vBST is associated with high anxiety. This is likely due to altered GABAergic and glutamatergic output that directly or indirectly modulates downstream brain areas promoting anxiety. I propose that contact with infants is a natural stimulus chronically down-regulating noradrenergic tone in the vBST. This downregulation of vBST noradrenergic tone is proposed to increase local GABA release, which disinhibits GABAergic projections and/or inhibits glutamatergic projections from the vBST to widespread areas of the brain, resulting in reduced maternal anxiety. Using postpartum laboratory rats as a model, this hypothesis will be tested by: 1) examining the effects of pharmacologically increasing or decreasing noradrenergic tone in the vBST on mothers'anxiety-related behaviors, 2) using in vivo microdialysis to measure extracellular norepinephrine release in the vBST while mothers interact with infants or are exposed to particular sensory cues from their infants, 3) using anatomical tracing to determine the neurochemical phenotype (GABAergic or glutamatergic) of projections from the vBST and other BST subregions to the central amygdala, supramammillary nucleus, and periaqueductal gray and 4) pharmacologically manipulating GABAA receptor activity in these three vBST target sites to determine if GABAA receptor modulation in these areas can prevent or mimic the effects of infant contact on mothers'anxiety-related behaviors. These experiments will be the first to examine the role of norepinephrine in the vBST, and its larger neural network, in the anxiety-reducing effects of infant contact. This information will greatly reinforce the notion that physical contact with infants positively modulates maternal neurochemistry and emotional state, and will improve the diagnosis and treatment of the millions of women and their infants affected each year by postpartum anxiety disorders.

Public Health Relevance

High postpartum anxiety has devastating effects on maternal motivation, mother-infant interactions, and infant development. Understanding the neural basis of how anxiety is regulated during the postpartum period is critically important for many women and their children. Determining how physical contact with infants modulates maternal neurochemistry in a way that alleviates anxiety will help improve the diagnosis and treatment of women suffering from a postpartum anxiety disorder.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Neurobiology of Motivated Behavior Study Section (NMB)
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Freund, Lisa S
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Michigan State University
Schools of Arts and Sciences
East Lansing
United States
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Holschbach, M Allie; Vitale, Erika M; Lonstein, Joseph S (2018) Serotonin-specific lesions of the dorsal raphe disrupt maternal aggression and caregiving in postpartum rats. Behav Brain Res 348:53-64
Grieb, Z A; Holschbach, M A; Lonstein, J S (2018) Interaction between postpartum stage and litter age on maternal caregiving and medial preoptic area orexin. Physiol Behav 194:430-436
Pawluski, Jodi L; Lonstein, Joseph S; Fleming, Alison S (2017) The Neurobiology of Postpartum Anxiety and Depression. Trends Neurosci 40:106-120
Holschbach, M Allie; Lonstein, Joseph S (2017) Motherhood and infant contact regulate neuroplasticity in the serotonergic midbrain dorsal raphe. Psychoneuroendocrinology 76:97-106
Grieb, Z A; Tierney, S M; Lonstein, J S (2017) Postpartum inhibition of ovarian steroid action increases aspects of maternal caregiving and reduces medial preoptic area progesterone receptor expression in female rats. Horm Behav 96:31-41
Agrati, Daniella; Lonstein, Joseph S (2016) Affective changes during the postpartum period: Influences of genetic and experiential factors. Horm Behav 77:141-52
Harding, Kaitlyn M; Lonstein, Joseph S (2016) Extensive juvenile ""babysitting"" facilitates later adult maternal responsiveness, decreases anxiety, and increases dorsal raphe tryptophan hydroxylase-2 expression in female laboratory rats. Dev Psychobiol 58:492-508
Ragan, Christina M; Harding, Kaitlyn M; Lonstein, Joseph S (2016) Associations among within-litter differences in early mothering received and later emotional behaviors, mothering, and cortical tryptophan hydroxylase-2 expression in female laboratory rats. Horm Behav 77:62-71
Lonstein, Joseph S; Lévy, Frédéric; Fleming, Alison S (2015) Common and divergent psychobiological mechanisms underlying maternal behaviors in non-human and human mammals. Horm Behav 73:156-85
Harding, Kaitlyn M; Lonstein, Joseph S (2014) Placentophagia in weanling female laboratory rats. Dev Psychobiol 56:1290-9

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