Chronic stress produces deficits in cognition accompanied by alterations in
neural chemistry and morphology. For example, both stress and chronic admi
nistration of corticosterone produce dendritic atrophy in hippocampal neuro
ns (Woolley C, Gould E, McEwen BS. 1990. Exposure to excess glucocorticoids
alters dendritic morphology of adult hippocampal pyramidal neurons. Brain
Res 531:225-231; Watanabe Y, Gould E, McEwen BS, 1992b. Stress induces atro
phy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 588
:341-345). Prefrontal cortex is also a target for glucocorticoids involved
in the stress response (Meaney MJ, Aitken DH. 1985. [H-3]Dexamethasone bind
ing in rat frontal cortex. Brain Res 328:176-180); it shows neurochemical c
hanges in response to stress (e.g., Luine VN, Spencer RL, McEwen BS. 1993.
Effect of chronic corticosterone ingestion on spatial memory performance an
d hippocampal serotonergic function. Brain Res 616:55-70; Crayton JW, Joshi
I, Gulati A, Arora RC, Wolf WA. 1996. Effect of corticosterone on serotoni
n and catecholamine receptors and uptake sites in rat frontal cortex. Brain
Res 728:260-262; Takao K, Nagatani T, Kitamura Y, Yamawaki S. 1997. Effect
s of corticosterone on 5-HT1A and 5-HT2 receptor binding and on the recepto
r-mediated behavioral responses of rats. Eur J Pharmacol 333:123-128; Sandi
C, Loscertales M. 1999. Opposite effects on NCAM expression in the rat fro
ntal cortex induced by acute vs. chronic corticosterone treatments. Brain R
es 828:127-134), and mediates many of the behaviors that are altered by chr
onic corticosterone administration (e.g., Lyons DM, Lopez JM, Yang C, Schat
zberg AF. 2000. Stress-level cortisol treatment impairs inhibitory control
of behavior in monkeys. J Neurosci 20:7816-7821). To determine if glucocort
icoid-induced morphological changes also occur in medial prefrontal cortex,
the effects of chronic corticosterone administration on dendritic morpholo
gy in this corticolimbic structure were assessed. Adult male rats received
s.c. injections of either corticosterone (10 mg in 250 muL sesame oil, n =
8) or vehicle (250 muL; n = 8) daily for 3 weeks. A third group of rats ser
ved as intact controls (n = 4). Brains were stained using a Golgi-Cox proce
dure and pyramidal neurons in layer II-III of medial prefrontal cortex were
drawn; dendritic morphology was quantified in three dimensions. Sholl anal
yses demonstrated a significant redistribution of apical dendrites in corti
costerone-treated animals: the amount of dendritic material proximal to the
soma was increased relative to intact rats, while distal dendritic materia
l was decreased relative to intact animals. Thus, chronic glucocorticoid ad
ministration dramatically reorganized apical arbors in medial prefrontal co
rtex. This reorganization likely reflects functional changes and may contri
bute to stress-induced changes in cognition. (C) 2001 John Wiley & Sons, In
c.