The Primate Animal Model Core (Core C) of the Emory University Center for Neuroscience of Mental Disorders (CNMD) will serve as the source of all non-human primates used by the individual preclinical Research Projects. In specific, Core C will produce and characterize a non-human primate epigenetic early life stress (ELS) model involving neonatal exposure of rhesus monkeys (Macaca mulatta) mother-infant dyads to low foraging (LFD) or variable foraging (VFD) demand for their daily food ration up for to three months. An immediate consequence of the stringent VF condition is a reduction in the amount of time mothers respond to infant solicitations for contact and attention. The VF condition permits normal social and physical development of infant monkeys but significantly increases their subsequent behavioral and physiological sensitivity to stressful challenges including sensitivity to noradrenergic and serotonergic anxiogenic drugs and persistent increases in CSF levels of CRF in adult monkeys. These findings indicate that ELS via VF rearing produces long-term increases in reactivity to stressful experience which are consistent with features of human psychiatric disorders. This procedure offers some important advantages and sources of validity: (l) the contingencies imposed by the paradigm are naturalistic, infant development is influenced by ecological demands on mother's availability, (2) the demands are imposed during a critical period of infant, behavioral development when infants normally solicit reassurance as they begin to explore their environment, (3) as found in some human psychopathologies, deficits are reflected in the capacity of monkeys to respond to stressful experiences as adults. Comparison of this primate model with the genetic and ELS rodent models (see Core B) will permit individual Center Research Projects to test the thesis that, in diverse species, similar neurocircuits and intracellular mechanisms are impacted by genetic and epigenetic factors across which give rise to depressive-like syndrome. Furthermore, the efficacy of various treatments (antidepressant, corticotropin releasing factor antagonist) in reversing aspects of depressive-like syndrome will be tested in this model. To this end, Core C will characterize the behavioral and HPA axis stress responsiveness of each animal as well as providing sampling services, surgical services such as CNS guide cannula implantation, chronic drug treatments, and necropsy to the individual Center Research Projects. This organization has the advantage of maintaining consistency in animal handling and implementation of all protocols so that each preclinical Research Project receives identically characterized and treated animals for study.
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