Figure.

Schematized drawing illustrating crosstalk between the hypothalamic corticotropin-releasing hormone (CRH)-pituitary-adrenal (HPA) and extrahypothalamic CRH (eCRH) stress axes. Brain neurotransmitters such as serotonin (5-hydroxytryptamine or 5-HT) and norepinephrine (NE) stimulate (+) these interconnected stress circuits, whereas endogenous opiates inhibit (–) stress responses. Solid lines indicate direct connections between the brain nuclei where these neurotransmitters are manufactured and the brain structure (e.g., the hippocampus) involved in modulating the stress response, and dashed lines indicate indirect connections between these structures. See text for details.