The in vivo proconvulsant effects of corticotropin releasing hormone in the developing rat are independent of ionotropic glutamate receptor activation.
Corticotropin releasing hormone (CRH) produces age-dependent limbic seizures in the infant rat. Both the phenotype and the neuroanatomic matrix of CRH-induced seizures resemble the seizures induced by the rigid glutamate analogue, kainic acid (KA), and by rapid amygdala kindling. The experiments described in this study tested the hypothesis that the in vivo proconvulsant effects of CRH require activation of ionotropic glutamate receptors. Non-competitive (+MK-801) or competitive (CGP-39551) antagonists of N-methyl-d-aspartate (NMDA) receptors decreased or eliminated the motor effects of CRH, but electrographic CRH-induced seizures were unaffected. Administration of CRH antagonists did not affect the acquisition or the maintenance of rapid kindling, which are mediated by NMDA and alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor activation, respectively. CRH receptor blockers failed to alter the latency or duration of seizures induced by activation of KA receptors, and threshold doses of CRH and KA had additive effects. CRH given repeatedly decreased the convulsant threshold dose of KA, probably via injury to hippocampal neurons. These results suggest that CRH and glutamate increase neuronal excitability via independent mechanisms. Because the proconvulsant effects of CRH are highly specific to the developmental period, glutamate-receptor-independent, CRH-receptor mediated excitation may account for some of the enhanced susceptibility to seizures during this period.
Brunson
K L
KL
Department of Anatomy/Neurobiology, University of California, Irvine, CA 92697, USA.
Schultz
L
L
Baram
T Z
TZ
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004056:Differential Threshold / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004569:Electroencephalography; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D006727:Hormone Antagonists; D017470:Receptors, Glutamate; D003346:Corticotropin-Releasing Hormone; D007608:Kainic Acid