Genetic Dissection of the Neuroendocrine and Behavioral Responses to Stressful Challenges

Excerpt

Dysregulation of the stress response is implicated in many psychopathologies. Data gathered over the past two decades have proposed a rather dualistic view of the central corticotropin-releasing factor (CRF)-urocortin system. Originally, it was thought that CRF/CRF receptor type 1 (CRFR1) signaling mediated stress-initiated effects and increased anxiety-like behavior, whereas activation of urocortins/CRFR2 ensured adequate recovery from stress and restoration of homeostasis. However, this view was based on data gained from genetically modified mouse models and pharmacological approaches; now, with the emergence of new and more specific biological tools, it has become clear that this is an over-simplistic proposal. It is becoming apparent that the function of the CRF-urocortin system’s components relies profoundly on the spatial and temporal patterns of activity of the CRF family members. Here, we provide an overview of recent work that proposes a more dynamic, modulatory role for the CRF system’s central pathways in the modulation of stress-linked behaviors. Recent findings suggest that the CRF system’s actions are brain-region specific and dependent on the type of neuronal cell involved.