Fig. 1.

A simplified diagram of the circuits involved in ‘physiological’ and ‘psychological’ stress responses. Physiological stress signals activate the neuroendocrine hypothalamic–pituitary–adrenal axis (outlined by the rectangular box). Physiological stress signals converge on the hypothalamic paraventricular nucleus (PVN) causing the release of corticotropin-releasing hormone (CRH) into the hypothalamo–pituitary portal system. CRH elicits secretion of adrenocorticotropic hormone (ACTH) from the pituitary and ACTH induces the release of glucocorticoids (GC) from the adrenal gland. GCs cross the blood–brain barrier and interact with type-2 corticoid receptors (GR) in the hippocampus, PVN and pituitary to ‘shut-off’ the neuroendocrine response to stress (indicated by the blunt-ended lines). In contrast, activation of GR in the central nucleus of the amygdala increases CRH expression in this region [30,113] and is generally considered to facilitate stress responses. Psychological stress engages additional brain regions and circuits, involving, at a minimum, the hippocampal formation. Arrows denote facilitatory projections.