Our group has developed a nonhuman primate model of adverse early rearing which results in long-standing anxiety-like behaviors accompanied by a range of biochemical alterations including alterations of concentrations of cerebrospinal fluid (CSF) neuropeptides, such as corticotrophin-releasing factor (CRF) and somatostatin (SOM), and monoamine metabolites of serotonin [5-hydroxy-indole-acetic acid (5-HIAA)] as well as dopamine [homovanillic acid (HVA)]. For this model, genetically random monkeys are reared as infants by mothers exposed to unpredictable variability in foraging demand (VFD). Of note, the neurochemical alterations observed in the VFD-reared primates bear resemblance to certain aspects of biogenic amine, neuropeptide and neuroendocrine disturbances observed in a number of clinical conditions. Our primary focus is that prefrontal cortical efferents, either directly or via thalamic nuclei efferents, utilize the glutamate neurotransmitter system and are hypothesized to be a primary source for neuronal stimulation of the """"""""fear"""""""" neurocircuitry. This fear network originates from the central nucleus of the amygdala (CeN) and bed nucleus of the stria terminalis (BNST). Both of these limbic structures contain particularly dense concentrations of CRF-producing neurons. We propose that excessive glutamatergic discharge consequent to adverse early rearing may provide a key contribution towards the hyper-excitation of these key neuronal populations which are involved in the behavioral manifestations of anxiety. Reduction in glutamatergic neurotransmission should therefore reduce anxiety levels and the concomitant biochemical alterations associated with VFD rearing. The major aim of this proposal is the pharmacological reduction of the anxious behavioral profile associated with VFD rearing through attenuation of the glutamatergic system, using a normative or low foraging demand (LFD)-reared control group. Ongoing neurochemical and behavioral assessments will provide extensive longitudinal documentation of the effects of such reductions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH059990-01A1
Application #
6127505
Study Section
Special Emphasis Panel (ZRG1-IFCN-2 (01))
Program Officer
Winsky, Lois M
Project Start
2000-07-05
Project End
2004-06-30
Budget Start
2000-07-05
Budget End
2001-06-30
Support Year
1
Fiscal Year
2000
Total Cost
$264,775
Indirect Cost
Name
Suny Downstate Medical Center
Department
Psychiatry
Type
Schools of Medicine
DUNS #
068552207
City
Brooklyn
State
NY
Country
United States
Zip Code
11203
Coplan, Jeremy D; Gopinath, Srinath; Abdallah, Chadi G et al. (2017) Effects of Acute Confinement Stress-induced Hypothalamic-Pituitary Adrenal Axis Activation and Concomitant Peripheral and Central Transforming Growth Factor-?1 Measures in Nonhuman Primates. Chronic Stress (Thousand Oaks) 1:
Kaufman, Joan; Gelernter, Joel; Hudziak, James J et al. (2015) The Research Domain Criteria (RDoC) Project and Studies of Risk and Resilience in Maltreated Children. J Am Acad Child Adolesc Psychiatry 54:617-25
Coplan, Jeremy D; Syed, Shariful; Perera, Tarique D et al. (2014) Glucagon-like peptide-1 as predictor of body mass index and dentate gyrus neurogenesis: neuroplasticity and the metabolic milieu. Neural Plast 2014:917981
Perera, Tarique D; Dwork, Andrew J; Keegan, Kathryn A et al. (2011) Necessity of hippocampal neurogenesis for the therapeutic action of antidepressants in adult nonhuman primates. PLoS One 6:e17600
Kinnally, Erin L; Feinberg, Caroline; Kim, David et al. (2011) DNA methylation as a risk factor in the effects of early life stress. Brain Behav Immun 25:1548-53
Coplan, Jeremy D; Abdallah, Chadi G; Kaufman, Joan et al. (2011) Early-life stress, corticotropin-releasing factor, and serotonin transporter gene: a pilot study. Psychoneuroendocrinology 36:289-93
Coplan, Jeremy D; Abdallah, Chadi G; Mathew, Sanjay J et al. (2011) Metabolic syndrome and neurometabolic asymmetry of hippocampus in adult bonnet monkeys. Physiol Behav 103:535-9
Abdallah, Chadi G; Tang, Cheuk Y; Mathew, Sanjay J et al. (2010) Diffusion tensor imaging in studying white matter complexity: a gap junction hypothesis. Neurosci Lett 475:161-4
Coplan, Jeremy D; Mathew, Sanjay J; Abdallah, Chadi G et al. (2010) Early-life stress and neurometabolites of the hippocampus. Brain Res 1358:191-9
Perera, Tarique D; Coplan, Jeremy D; Lisanby, Sarah H et al. (2007) Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates. J Neurosci 27:4894-901

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