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. 1991 Jul 16;61(1):97-101.
doi: 10.1016/0165-3806(91)90118-3.

Corticotropin-releasing hormone is a rapid and potent convulsant in the infant rat

T Z Baram  1 , L Schultz
Affiliations

Corticotropin-releasing hormone is a rapid and potent convulsant in the infant rat

T Z Baram et al. Brain Res Dev Brain Res. .

Abstract

Corticotropin-releasing hormone (CRH) administered into the cerebral ventricles of rats during the first postnatal week caused a specific and stereotyped behavior sequence: rhythmic chewing and licking (jaw myoclonus) were followed by 'limbic'-type seizures. The onset of the seizures was much more rapid (2-45 min vs 3-7 h) than in adult rats, and the convulsant doses were much lower (50 x 10(-12) mol per gram brain weight vs 750 x 10(-12) mol per gram brain weight in adults). CRH potency in inducing seizures varied inversely with age. CRH-induced seizures occurred prior to any changes in serum corticosterone, and were eliminated by the administration of a CRH antagonist, as well as of phenytoin. Electrocorticographic correlates of CRH-induced behaviors in the infant rat were inconsistent, suggesting a subcortical origin of CRH-induced paroxysmal events in the immature brain.

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Figures

Fig. 1
Fig. 1
Photograph of a 5-day-old male rat pup displaying jaw and tongue myoclonus, following CRH (150 × 10−12 mol) administration into the cerebral ventricles.
Fig. 2
Fig. 2
Age dependence of seizure-inducing doses of CRH. Details of motor phenomena are given in the text. Numbers in brackets denote number of animals per group.
Fig. 3
Fig. 3
Electrocorticograms of 5-day-old rat pups, before (A) and 20 minutes after (B) intracerebroventricular (i.c.v.) administration of 22.5 × 10−12 mol CRH. C: 20 min after CRH administration, in a rat given alpha-helical CRH (10 mcg, i.c.v.) 40 min prior to the peptide. ECoG, electrocorticogram; EKG, electrocardiogram; EMG, recording from an electrode placed over angle of jaw, anterior to the ear. Horizontal bars = 1 s. Vertical bars = 50 µV.
Fig. 4
Fig. 4
Plasma corticosterone in infant rats subjected to CRH (0.15 nmol, filled circles) or saline (open circles) injection into the cerebral ventricles (i.c.v.). At the 30 min time-point, CRH-injected rats have begun having motor phenomena, which were well established by 45 min. Bars denote standard errors; *P < 0.05.
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References

    1. Aicardi J. Infantile spasms and related syndromes. In: Aicardi J, editor. Epilepsy in Children. New York: Raven Press; 1986. pp. 17–38.
    1. Albala BJ, Moshe SL, Okada R. Kainic acid-induced seizures: a developmental study. Dev. Brain Res. 1984;13:139–148. - PubMed
    1. Baram TZ, Citron M, Schultz L. CRH in frog retina — quantitative and detailed anatomical analysis. Soc. Neurosci. 1988 Abs. 19.13.
    1. Baram TZ, Schultz L. Fetal and maternal plasma corticosterone and ACTH after pharmacological adrenalectotmy. Life Sci. 1990;47:485–489. - PubMed
    1. Baram TZ, Schultz L. The ontogeny of somatostatin gene expression in rat diencephalon. Dev. Neurosci. in press. - PubMed

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