Forty-five years after its discovery, brain serotonin (5-HT) is still the s
ubject of intense research aimed at understanding ifs role in stress adapta
tion. At the presynaptic level, numerous stressors increase nerve firing an
d extracellular 5-HT at the level of serotonergic cell bodies or nerve term
inals. Different studies have reported stressor- and region-specific change
s in extracellular 5-HT, a view challenged by electrophysiological and neur
ochemical evidence for a nonspecific response of serotonergic neurones to s
tressors when activity/arousal is taken into account. In addition, early st
udies indicate that stress-induced elevation in 5-HT synthesis, a key count
er-regulatory process allowing serotonergic homeostasis, is mediated by spe
cific neuroendocrine mechanisms. In addition to the multiplicity of postsyn
aptic 5-HT receptors and their specific regulation by corticoids, specifici
ty to stressors is also underscored when considering one receptor type such
as the 5-HT1A receptor. Stress studies should consider the past experience
and the genetic status of the individual as key modulators oft he serotone
rgic responses to stress. (C) 1999 American College of Neuropsychopharmacol
ogy. Published by Elsevier Science Inc.