Effects of amygdala kindling and electroconvulsive seizures on the expression of corticotropin-releasing hormone in the rat brain.
Wjile low doses of corticotropin-releasing hormone (CRH) induce behavioral activation as part of the stress response, higher doses cause pathological excitability and seizures. Single CRH-induced convulsions resemble those following amygdala "kindling" in which intermittent exposure to a subconvulsive electrical stimulus eventually produces a motor seizure. To examine the possibility that alterations in CRH activity occur in kindling we used in situ hybridization to determine if electrical kindling of the amygdala or electroconvulsive seizures (ECS) could alter the expression of CRH mRNA in the rat brain. Amygdala kindling resulting in either after-discharges alone or full-blown motor seizures produced a dramatic increase in CRH but not glutamic acid decarboxylase (GAD) mRNA in the dorsal hippocampus, specifically in the large interneurons of the polygonal layer of the dentate hilus. CRH mRNA per cell and the number of cells expressing CRH increased at 30 min, 2 h, and 24 h but not at 3 weeks following the last kindled seizure. Repeated ECS also induced an up-regulation of CRH mRNA in the dentate hilus. Immunohistochemistry confirmed that seizures increased the number of hilar cells expressing CRH peptide. This induction of CRH could not be explained by nonspecific stress effects as neither restraint stress nor adrenalectomy had any influence on CRH mRNA in the dentate hilus. Both repeated ECS and kindled seizures also caused an increase in CRH mRNA in the hypothalamic paraventricular nucleus similar to that induced by chronic stress. Our results indicate that epileptiform activity induces CRH mRNA in the dentate hilus where normally very little CRH is expressed, suggesting that CRH may be important in mediating electrical excitability in the dentate gyrus and hippocampus.
Smith
M A
MA
Clinical Neuroendocrinology Branch, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA.
Weiss
S R
SR
Abedin
T
T
Kim
H
H
Post
R M
RM
Gold
P W
PW