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Corticotropin-releasing hormone is a rapid and potent convulsant in the infant rat
Insights
Corticotropin-releasing hormone (CRH) in infant rats triggers rapid seizures and jaw myoclonus. This effect is age-dependent and suggests a subcortical origin in the developing brain.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Corticotropin-releasing hormone (CRH) plays a crucial role in the stress response.
- The effects of CRH on the immature brain are not fully understood.
- Early postnatal development is a critical period for neural circuit maturation.
Purpose of the Study:
- To investigate the effects of CRH administration in the infant rat brain.
- To characterize the behavioral and electrophysiological responses to CRH in early development.
- To compare CRH's convulsant potency in infant versus adult rats.
Main Methods:
- Intracerebroventricular administration of CRH in first-week postnatal rats.
- Behavioral observation for stereotyped sequences including jaw myoclonus and limbic seizures.
- Comparison of seizure onset time and effective doses with adult rats.
- Administration of CRH antagonist and phenytoin to assess blockade and anticonvulsant effects.
- Electrocorticographic recordings to correlate brain activity with behaviors.
Main Results:
- CRH induced a specific sequence of jaw myoclonus followed by limbic seizures in infant rats.
- Seizure onset was significantly faster and required lower doses in infant rats compared to adults.
- CRH potency for seizure induction showed an inverse relationship with age.
- CRH-induced seizures preceded serum corticosterone changes and were blocked by CRH antagonists and phenytoin.
- Electrocorticography showed inconsistent correlates, suggesting subcortical origins of CRH-induced events.
Conclusions:
- CRH is a potent convulsant in the immature rat brain, acting via a subcortical mechanism.
- The developing brain exhibits heightened sensitivity to CRH-induced seizures.
- These findings highlight the critical role of CRH in early neurodevelopment and seizure susceptibility.
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.