Defensive behaviors motivated by fear protect organism from danger; but intense fearfulness or activation of inappropriate defensive behaviors can result in behavioral, social, and physiological dysfunction. In young rhesus monkeys we have characterized three patterns of defensive behavior, discovered the environmental cues that elicit them, and developed a model for studying their differential regulation. Preliminary studies suggest that expression of these behaviors is regulated by opiate, benzodiazepine, and CRH systems. The objective of the proposed studies is to determine the developmental time course of infant monkeys' defensive behavioral and endocrine responses and to examine the neurochemical regulation of their expression. Our paradigm elicits defensive responses under 3 conditions: ALONE (infants briefly separated from their mothers, resulting in a high rate of species- species distress calls), and two conditions involving environmental threat. In NO EYE CONTACT, infants are separated from their mothers and exposed to a videotaped human face in profile, resulting in behavioral inhibition and reduced distress calls. In STARE, separated infants are exposed to a videotape of the same face neutrally looking directly ahead, resulting in barking and aggressive gestures. The studies are in three parts. Part I examines the ontogeny of the rhesus monkey's behavioral and endocrine defensive responses. This will establish the age at which infants away from their mothers can discriminate relevant threatening stimuli and express adaptive defensive responses. Part II tests whether prior experience with the threatening situation modulates behavioral and endocrine responses. Part III utilizes dose-response studies with selective agents to assess the roles of opiate, benzodiazepine, and CRH systems in regulating defensive behaviors and endocrine responses. Our model is highly relevant to human emotional development and fear- related behavior. It lets us examine the developmental and neurochemical factors mediating appropriate expression of defensive behaviors in primates. Understanding these behaviors may provide insight into mechanisms involved in the onset of stranger anxiety, temperamental differences in personality development, and development of anxiety-related psychopathology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH046729-03
Application #
3386569
Study Section
Psychobiology and Behavior Review Committee (PYB)
Project Start
1990-07-01
Project End
1993-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Fox, Andrew S; Oler, Jonathan A; Birn, Rasmus M et al. (2018) Functional Connectivity within the Primate Extended Amygdala Is Heritable and Associated with Early-Life Anxious Temperament. J Neurosci 38:7611-7621
Zhao, Gengyan; Liu, Fang; Oler, Jonathan A et al. (2018) Bayesian convolutional neural network based MRI brain extraction on nonhuman primates. Neuroimage 175:32-44
Kalin, Ned H (2018) Corticotropin-Releasing Hormone Binding Protein: Stress, Psychopathology, and Antidepressant Treatment Response. Am J Psychiatry 175:204-206
Alisch, Reid S; Van Hulle, Carol; Chopra, Pankaj et al. (2017) A multi-dimensional characterization of anxiety in monozygotic twin pairs reveals susceptibility loci in humans. Transl Psychiatry 7:1282
Shackman, A J; Fox, A S; Oler, J A et al. (2017) Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology. Mol Psychiatry 22:724-732
Oler, Jonathan A; Tromp, Do P M; Fox, Andrew S et al. (2017) Connectivity between the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the non-human primate: neuronal tract tracing and developmental neuroimaging studies. Brain Struct Funct 222:21-39
Kalin, Ned H (2017) Mechanisms underlying the early risk to develop anxiety and depression: A translational approach. Eur Neuropsychopharmacol 27:543-553
Kalin, Ned H; Fox, Andrew S; Kovner, Rothem et al. (2016) Overexpressing Corticotropin-Releasing Factor in the Primate Amygdala Increases Anxious Temperament and Alters Its Neural Circuit. Biol Psychiatry 80:345-55
Fox, Andrew S; Oler, Jonathan A; Shackman, Alexander J et al. (2015) Intergenerational neural mediators of early-life anxious temperament. Proc Natl Acad Sci U S A 112:9118-22
Cavanagh, James F; Shackman, Alexander J (2015) Frontal midline theta reflects anxiety and cognitive control: meta-analytic evidence. J Physiol Paris 109:3-15

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