When Nerve Growth Factor Met Behavior.

Since its first characterization in the early 1950s, the role of the polypeptidic nerve growth factor (NGF) in controlling behavior remained elusive. Since the mid-1980s, we undertook a series of experiments aimed at elucidating the biological role(s) played by neurotrophins, particularly NGF, in adult rodents. At the beginning, we concentrated on the submandibular salivary gland of the male mouse, which was known to store massive amount of NGF. We found that under specific stress conditions, the salivary NGF is released in the bloodstream: intermale fighting between isolated males was the first reported context in which salivary NGF was released, thus providing a physiological significance for its presence in the adult, territorial males. We also found that dominant males release less NGF than subordinates and provided a loop-type model which includes intermale social confrontation, adrenal gland size, and functional status, corticosterone release, a model resulting in likelihood to be stabilized in a "dominant" or a "subordinate" social status. A variety of social anxiety contexts of mammals, humans included, has been described since then, and further studies carried out on humans showed that NGF is released in the bloodstream of parachutists at their first skydiving experience and in the case of ranking high on the Passionate Love Scale (amour fou). Ethological data from lab rodents helped in understanding NGF function in subtly controlling social "status" of male mice: the considerations about the interplay among neurobiological, physiological, and behavioral factors in structuring the dominant vs subordinate phenotypes may well apply to other vertebrate species, specifically addressing the underlying role of neurotrophins in relating behavior and brain neuroplasticity.