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Intraspecific fighting induced by 6-8 weeks of social isolation results in massive release of nerve growth factor (NGF) into the bloodstream of adult male mice. The amount of circulating NGF is highly correlated with the number of fighting episodes. Biological, radioimmunological, immunohistochemical, and ultrastructural studies show that NGF is discharged from the salivary gland into the blood within minutes after fighting and reaches the highest level 3-4 hr later. Adrenergic innervation of the salivary gland or adrenalectomy does not abolish the NGF release. Corticotropic hormones do not induce NGF increase in the blood. Daily administrations of highly purified NGF (3 micrograms per g of body weight) result in a considerable increase in the volume of adrenal glands. These findings are unequivocable evidence for a physiological role of the mouse salivary glands as a major source of blood NGF.

Aggressive behavior induces release of nerve growth factor from mouse salivary gland into the bloodstream.