THE IN-VIVO PROCONVULSANT EFFECTS OF CORTICOTROPIN-RELEASING HORMONE IN THE DEVELOPING RAT ARE INDEPENDENT OF IONOTROPIC GLUTAMATE-RECEPTORACTIVATION

Corticotropin releasing hormone: (CRH) produces age-dependent limbic s eizures in the infant rat. Both the phenotype and the neuroanatomic ma trix of CRH-induced seizures resemble the seizures induced by the rigi d glutamate analogue, kainic acid (KA), and by rapid amygdala kindling . The experiments described in this study tested the hypothesis that t he in vivo proconvulsant effects of CRH require activation of ionotrop ic 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-induce d seizures were unaffected. Administration of CRH :antagonists did not affect the acquisition or the maintenance of rapid kindling, which ar e mediated by NMDA and ha-amino-3-hydroxy-5-methyl-isoxazole-4-propion ate (AMPA) receptor activation, respectively. CRH receptor blockers fa iled to alter the latency or duration of seizures induced by activatio n of KA receptors, and threshold doses of CRH and KA had additive effe cts. CRH given repeatedly decreased the convulsant threshold dose of K A, probably via injury to hippocampal neurons. These results suggest t hat CRH and glutamate increase neuronal excitability via independent m echanisms. Because the proconvulsant effects of CRH are highly specifi c to the developmental period, glutamate-receptor-independent, CRH-rec eptor mediated excitation may account for some of the enhanced suscept ibility to seizures during this period. (C) 1998 Elsevier Science B.V. All rights reserved.