Translating stress systems: corticotropin releasing factor, its receptors, and the dopamine system in nonhuman primate models.

Abstract

Stress is a fact of life, affecting organisms from the smallest invertebrates to humans. Mediating the stress system is the ancient neuropeptide, corticotropin releasing factor (CRF), which works as a neuromodulator to alter brain systems and homeostatic responses to stress. In humans, many stress-related psychiatric illnesses are linked to dysregulation of monoamine systems, which have cross-talk with CRF-enriched circuits. In this review, we focus on the CRF and the midbrain dopamine (DA) system, particularly as it relates to the nonhuman primate. While tremendous knowledge of CRF-DA mechanisms has been gleaned from rodent models, treatments for stress-related diseases have been elusive, raising the question of whether higher animal models might be required. Subtle shifts in CRF peptide or CRF receptor localization, and the expansion and complexity of DA neuron populations, may hold some of the keys to understanding long-standing stress effects on the DA system in humans. Our laboratory has especially been interested in laying out the neural architecture of the CRF-DA system interface in the nonhuman primate, as a close anatomic model for human. Using rodent models as a starting point, we describe aspects of this complex system that inform our understanding of CRF-DA interactions, and focus on results that have been, and those that still need to be, translated to nonhuman primate models.