The proposed research is designed to study the long term consequences of being exposed to psychosocial stress (episodic vs. chronic) during infancy using a well controlled nonhuman primate model. It is based upon two recent findings from this laboratory's mother-infant (m-i) research program. First, we have found that squirrel monkey infants that had experienced repeated brief m-i separations prior to weaning displayed an earlier onset of puberty and a reduced biobehavioral response to the stress of social isolation when examined as juveniles. Second, we have established a paradigm that produces chronic stress that can be imposed m-i squirrel monkey dyads to study the long term effects of chronic stress during infancy. Increasing the difficulty to obtain food (without restricting the amount of food consumed) resulted in chronic elevation of plasma cortisol levels in both mother infants, and disruption of social relationships.
The specific aims of this proposal are: 1) To assess the long term consequences of exposure to the acute and episodic stress of repeated m-i separations. We will investigate whether these effects are simply a response to removal from the mother or whether the degree of the stress associated with the separation is important. The length of separation and the environment into which the infant is placed following separation will be varied in ways that have been shown to increase or decrease the indices of stress. In addition to studying the undisturbed behavioral and physiological development of these differentially-reared monkeys, we will assess their biobehavioral responses to a variety of psychosocial stimuli (e.g., social isolation, exposure to a novel stimuli in the home cage, placement in a novel environment alone or with unfamiliar conspecifics) beginning at weaning and continuing through early adulthood. 2) To investigate the long term consequences of exposure to chronic stress during infancy. Specifically, this study will assess the long term effects of the stress associated with being reared under conditions of increased difficulty to obtain food. These offspring will be subjected to a similar battery of tests as referred to above. 3) To examine the interaction of the acute stress of m-i separation with the chronic stress of increased difficulty to obtain food. In addition to determining the long term consequences of being separated under a chronic stressful environment, this study will examine the immediate response of the m-i dyad to the challenge of brief separation and its subsequent effect on the m-i relationship upon reunion under conditions of chronic stress.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH047573-01A1
Application #
3387401
Study Section
Psychobiology and Behavior Review Committee (PYB)
Project Start
1991-09-30
Project End
1996-08-31
Budget Start
1991-09-30
Budget End
1992-08-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Lee, Alex G; Hagenauer, Megan; Absher, Devin et al. (2017) Stress amplifies sex differences in primate prefrontal profiles of gene expression. Biol Sex Differ 8:36
Lee, Alex G; Capanzana, Roxanne; Brockhurst, Jacqueline et al. (2016) Learning to cope with stress modulates anterior cingulate cortex stargazin expression in monkeys and mice. Neurobiol Learn Mem 131:95-100
Lee, Alex G; Buckmaster, Christine L; Yi, Esther et al. (2014) Coping and glucocorticoid receptor regulation by stress inoculation. Psychoneuroendocrinology 49:272-9
Murphy Jr, Greer M; Sarginson, Jane E; Ryan, Heather S et al. (2013) BDNF and CREB1 genetic variants interact to affect antidepressant treatment outcomes in geriatric depression. Pharmacogenet Genomics 23:301-13
Kelley, Ryan; Garrett, Amy; Cohen, Jeremy et al. (2013) Altered brain function underlying verbal memory encoding and retrieval in psychotic major depression. Psychiatry Res 211:119-26
Parker, Karen J; Buckmaster, Christine L; Lindley, Steven E et al. (2012) Hypothalamic-pituitary-adrenal axis physiology and cognitive control of behavior in stress inoculated monkeys. Int J Behav Dev 36:
Zeitzer, Jamie M; Kodama, Tohru; Buckmaster, Christine L et al. (2012) Time-course of cerebrospinal fluid histamine in the wake-consolidated squirrel monkey. J Sleep Res 21:189-94
Parker, Karen J; Maestripieri, Dario (2011) Identifying key features of early stressful experiences that produce stress vulnerability and resilience in primates. Neurosci Biobehav Rev 35:1466-83
Parker, Karen J; Hyde, Shellie A; Buckmaster, Christine L et al. (2011) Somatic and neuroendocrine responses to standard and biologically salient acoustic startle stimuli in monkeys. Psychoneuroendocrinology 36:547-56
Lee, Alex G; Cool, David R; Grunwald Jr, William C et al. (2011) A novel form of oxytocin in New World monkeys. Biol Lett 7:584-7

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