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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IFCN-2 (01))
Program Officer
Winsky, Lois M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Suny Downstate Medical Center
Schools of Medicine
United States
Zip Code
Coplan, Jeremy D; Gupta, Nishant K; Flynn, Sarah K et al. (2018) Maternal Cerebrospinal Fluid Glutamate in Response to Variable Foraging Demand: Relationship to Cerebrospinal Fluid Serotonin Metabolites in Grown Offspring. Chronic Stress (Thousand Oaks) 2:
Coplan, Jeremy D; Lu, Dunyue; El Sehamy, Alexander M et al. (2018) Early Life Stress Associated With Increased Striatal N-Acetyl-Aspartate: Cerebrospinal Fluid Corticotropin-Releasing Factor Concentrations, Hippocampal Volume, Body Mass and Behavioral Correlates. Chronic Stress (Thousand Oaks) 2:
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

Showing the most recent 10 out of 16 publications