Phenytoin prevents stress- and corticosterone-induced atrophy of CA3 pyramidal neurons.
Repeated daily restraint stress and daily corticosterone administration to adult male Sprague-Dawley rats leads to decreases in the number of branch points and length of dendrites of CA3 pyramidal neurons of the hippocampal formation. This decrease is prevented by daily administration of the antiepileptic drug phenytoin (Dilantin), which is known to interfere with excitatory amino acid release and actions. Phenytoin had no obvious effect on behavior during and after stress and failed to prevent stress-induced reduction of body weight gain and stress-induced increases of adrenal weight relative to body weight; it also failed to attenuate glucocorticoid-induced diminution of the size of the thymus gland, indicating that it does not directly antagonize glucocorticoid actions. Stress- and corticosterone-induced effects on dendritic length and branch point number are more pronounced on the apical, as opposed to the basal, CA3 dendrites that receive the largest mossy fiber input from the dentate gyrus. Because phenytoin is also known to prevent ischemic damage, these results are consistent with a model in which stress- and corticosterone-induced CA3 dendritic atrophy is produced by excitatory amino acids released from the mossy fibers.
Watanabe
Y
Y
Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021.
Gould
E
E
Cameron
H A
HA
Daniels
D C
DC
McEwen
B S
BS
D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D001284:Atrophy; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000633:toxicity*; D003712:Dendrites / Q000187:drug effects / Q000648:ultrastructure; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D010672:Phenytoin / Q000494:pharmacology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000473:pathology*
D010672:Phenytoin; D003345:Corticosterone