Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors.
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.
Magariños
A M
AM
Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021, USA.
McEwen
B S
BS
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001284:Atrophy; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D003489:Cyanoketone / Q000494:pharmacology; D003712:Dendrites / Q000648:ultrastructure*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism* / Q000473:pathology*
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D017470:Receptors, Glutamate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C087755:CGP 43487; D003489:Cyanoketone; D015763:2-Amino-5-phosphonovalerate; D003345:Corticosterone