Repeated restraint stress of rats for 21 days causes
atrophy of apical dendrites of hippocampal CA3c pyramidal neurons. This effect is mimicked by daily
corticosterone treatment for 21 days and is prevented y the anti-epileptic
drug,
phenytoin, known to interfere with
excitatory amino acid release and action. The present study was designed to investigate the involvement of endogenous
corticosterone secretion and
excitatory amino acid receptors in the stress-induced hippocampal dendritic
atrophy. Treatment of chronically stressed rats with the
steroid synthesis blocker
cyanoketone prevented stress-induced dendritic
atrophy.
Cyanoketone-treated animals showed an impaired
corticosterone secretion in response to the stressor, while basal levels were maintained. Besides the involvement of endogenous
corticosterone secretion,
N-methyl-D-aspartate receptors also play a role, since the competitive receptor antagonist,
CGP 43487, blocked stress-induced dendritic
atrophy. In contrast,
NBQX, a competitive inhibitor of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole
propionic acid receptors, was ineffective at a dose that blocks ischemic damage. These results indicate that the reversible
atrophy induced by 21 days of daily restraint stress requires
corticosterone secretion and that excitatory mechanisms involving
N-methyl-D-aspartate receptors play a major role in driving the
atrophy.