FIGURE 1 | The corticotropin-releasing factor system in depression.

From the following article:

New approaches to antidepressant drug discovery: beyond monoamines

Olivier Berton & Eric J. Nestler

Nature Reviews Neuroscience 7, 137-151 (February 2006)


New approaches to antidepressant drug discovery: beyond monoamines

Corticotropin-releasing factor (CRF) from the paraventricular nucleus (PVN) of the hypothalamus is released into the hypophyseal portal system and triggers the release of corticotropin (ACTH) from the anterior pituitary via stimulation of CRF1 receptors. ACTH, in turn, stimulates the secretion of glucocorticoid hormones (cortisol in humans or corticosterone in rodents) from the adrenal cortex. Increased glucocorticoid levels suppress hypothalamic CRF expression via negative feedback through hippocampal and hypothalamic glucocorticoid receptors. The neurotransmitter action of CRF on CRF1 receptors throughout the limbic system mediates anxiogenic effects of stress. By contrast, its neurotransmitter action on CRF2 receptors in more discrete regions of the brain might reduce anxiety-like behaviour in a delayed fashion. Amy, amygdala; BNST, bed nucleus of the stria terminalis; DR, dorsal raphe; HPA, hypothalamic–pituitary–adrenal; LDT, laterodorsal tegmental nucleus; LH, lateral hypothalamus; Pit, pituitary; Thal, thalamus.

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