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Short Interval Electrical Amygdala Kindling in Infant Rats

The Paradigm and Its Application to the Study of Age-Specific Convulsants

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Kindling 5

Part of the book series: Advances in Behavioral Biology ((ABBI,volume 48))

Abstract

Kindling is a powerful paradigm for investigating seizure generation, propagation and generalization. Kindling has been extensively utilized as a model of limbic seizures in the adult rat, and its reproducibility and precision are also particularly useful for the study of epilepsy in the developing brain. In the juvenile rat (>15 days), the refractory period between stimuli is much shorter than in the adult, potentially reflecting the increased excitability of the immature brain during this developmental period. “Rapid” or short-interval amygdala kindling of juvenile rats has been characterized and studied extensively.

The neuropeptide, corticotropin releasing hormone (CRH), produces limbic seizures in adult rodents, with a latency of 7–9 hours. The temporal and behavioral similarities between CRH-induced seizures and electrical amygdala kindling have suggested a common mechanism. In the infant rat (7–14 days), intracerebroventricular (icv) administration of picomolar doses of CRH produces amygdala-origin prolonged seizures with a very short latency (two minutes). The goals of studies described in this report were: a) to determine whether the rapid amygdala kindling paradigm could be applied to infant rats. b) to characterize the behavioral and electrical parameters of the kindling paradigm at this age. c) to study the interaction of CRH-induced seizures and amygdala kindling during infancy in the rat.

Using the short-interval-kindling method, Stage 5 behavioral seizures were achieved even in 7-day-old pups. However, the progression of behavioral kindling was different from that of older rats, and the correlation between electrographic after-discharges and behavioral stages was inversely related to age. Reliable, progressive amygdala afterdis-charges were difficult to ascertain in many animals prior to postnatal day 9. Spontaneous seizures occurred relatively frequently in younger age groups. Administration of a specific blocker of CRH receptors either icy or into the amygdala did not alter the rate of kindling development. Once stage 5 seizures were achieved, blocking CRH-receptors did not affect the expression of these seizures.

In conclusion, electrical amygdala kindling using short inter-stimulus intervals is a reliable and reproducible paradigm in rats during the second postnatal week, suggesting significant functional maturity of the amygdala-limbic circuitry at this age. The data provide no evidence for a mechanistic interaction between amygdala kindling and amygdalaorigin CRH-induced seizures in the developing rat.

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Author information

Authors and Affiliations

  1. Departments of Pediatrics, Anatomy, and Neurobiology and Neurology, University of California, Irvine, Irvine, California, USA

    Tallie Z. Baram & Linda Schultz

  2. INSERM U 398, Strasbourg, France

    Edouard Hirsch

Authors
  1. Tallie Z. Baram
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  2. Edouard Hirsch
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  3. Linda Schultz
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Editors and Affiliations

  1. University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    Michael E. Corcoran

  2. Albert Einstein College of Medicine, Bronx, New York, USA

    Solomon L. Moshé

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Baram, T.Z., Hirsch, E., Schultz, L. (1998). Short Interval Electrical Amygdala Kindling in Infant Rats. In: Corcoran, M.E., Moshé, S.L. (eds) Kindling 5. Advances in Behavioral Biology, vol 48. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5375-5_4

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  • DOI: https://doi.org/10.1007/978-1-4615-5375-5_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7453-4

  • Online ISBN: 978-1-4615-5375-5

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