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Experimental Brain Research

, Volume 81, Issue 2, pp 433–437 | Cite as

Seizure suppression in kindling epilepsy by intrahippocampal locus coeruleus grafts: evidence for an alpha-2-adrenoreceptor mediated mechanism

  • J. Bengzon
  • M. Kokaia
  • P. Brundin
  • O. Lindvall
Regular Papers

Summary

Intrahippocampal cell suspension grafts, prepared from the locus coeruleus region of rat fetuses, have previously been shown to retard seizure development in rats made hypersensitive to hippocampal kindling by a lesion of the forebrain noradrenergic system. The objective of the present study was to provide evidence that the seizure-suppressant effect elicited by the grafts is mediated via noradrenergic mechanisms. Two groups of rats received 6-hydroxydopamine in the lateral ventricle and then bilateral intrahippocampal locus coeruleus grafts. After 3 months, the grafted animals and a group of normal rats were subjected to hippocampal kindling. One group of grafted animals and the normal rats were injected intraperitoneally with the alpha-2 adrenergic receptor blocker idazoxan before each kindling stimulation. The other grafted rats received vehicle injections. The development of seizures was significantly faster in the grafted and normal rats that had been given idazoxan than in the grafted rats that had not been subjected to alpha-2 receptor blockade. Our data suggest that the seizure-suppressant action exerted by grafts of fetal locus coeruleus in hippocampal kindling is mediated via noradrenergic mechanisms, most likely via activation of postsynaptic alpha-2 adrenoreceptors.

Key words

Kindling Hippocampus Neural transplantation Locus coeruleus Idazoxan Rat 

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References

  1. Abercrombie M (1946) Estimation of nuclear population from microtome sections. Anat Rec 94:239–247Google Scholar
  2. Barry DI, Kikvadze I, Brundin P, Bolwig TG, Björklund A, Lindvall O (1987) Grafted noradrenergic neurons suppress seizure development in kindling-induced epilepsy. Proc Natl Acad Sci USA 84:8712–8715Google Scholar
  3. Bengzon J, Brundin P, Kalén P, Kokaia M, Lindvall O (1990) Host regulation of noradrenaline release from grafts of seizuresuppressant locus coeruleus neurons. Exp Neurol (in press)Google Scholar
  4. Björklund A, Lindvall O, Isacson O, Brundin P, Wictorin K, Strecker RE, Clarke DJ, Dunnett SB (1987) Mechanisms of action of intracerebral neural implants: studies on nigral and striatal grafts to the lesioned striatum. Trends Neurosci 10:509–516Google Scholar
  5. Björklund A, Nornes H, Gage FH (1986) Cell suspension grafts of noradrenergic locus coeruleus neurons in rat hippocampus and spinal cord: Reinnervation and transmitter turnover. Neuroscience 18:685–698Google Scholar
  6. Bortolotto ZA, Cavalheiro EA (1986) Effect of DSP4 on hippocampal kindling in rats. Pharmacol Biochem Behav 24:777–779Google Scholar
  7. Breese GR (1975) Chemical and immunochemical lesions by specific neurotoxic substances and antisera. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, Vol 1. Plenum, New York, pp 137–189Google Scholar
  8. Callaghan DA, Schwark WS (1979) Involvement of catecholamines in kindled amygdaloid convulsions in the rat. Neuropharmacology 18:541–545Google Scholar
  9. Carre G, Harley C (1986) DSP-4 treatment accelerates kindling. Exp Neurol 94:812–816Google Scholar
  10. Chauvel P, Trottier S (1986) Role of noradrenergic ascending system in extinction of epileptic phenomena. Adv Neurol 44:475–487Google Scholar
  11. Corcoran ME, Mason ST (1980) Role of forebrain catecholamines in amygdaloid kindling. Brain Res 190:473–484Google Scholar
  12. Gellman RL, Kallianos JA, McNamara JO (1987) Alpha-2 receptors mediate an endogenous noradrenergic suppression of kindling development. J Pharmacol Exp Ther 241:891–898Google Scholar
  13. Jimenez-Rivera C, Voltura A, Weiss GK (1987) Effect of locus coeruleus stimulation on the development of kindled seizures. Exp Neurol 95:13–20Google Scholar
  14. Kokaia M, Bengzon J, Kalén P, Lindvall O (1989a) Noradrenergic mechanisms in hippocampal kindling with rapidly recurring seizures. Brain Res 491:398–402Google Scholar
  15. Kokaia M, Kalén P, Bengzon J, Lindvall O (1989b) Noradrenaline and 5-hydroxytryptamine release in the hippocampus during seizures induced by hippocampal kindling stimulation: an in vivo microdialysis study. NeuroscienceGoogle Scholar
  16. Lorén I, Björklund A, Falck B, Lindvall O (1980) The aluminumformaldehyde (ALFA) histofluorescence method for improved visualization of catecholamines and indoleamines. 1. A detailed account of the methodology for central nervous tissue using paraffin, cryostat or vibratome sections. J Neurosci Meth 2:277–300Google Scholar
  17. McIntyre DC, Saari M, Pappas BA (1979) Potentiation of amygdala kindling in adult or infant rats by injections of 6-hydroxy-dopamine. Exp Neurol 63:527–544Google Scholar
  18. McIntyre DC, Edson N (1981) Facilitation of amygdala kindling after norepinephrine depletion with 6-hydroxydopamine in rats. Exp Neurol 74:748–757Google Scholar
  19. McIntyre DC, Edson N, Chao G, Knowles V (1982) Differential effect of acute vs chronic desmethylimipramine on the rate of amygdala kindling. Exp Neurol 78:158–166Google Scholar
  20. McIntyre DC, Giugno L (1988) Effect of clonidine on amygdala kindling in normal and 6-hydroxydopamine-pretreated rats. Exp Neurol 99:96–106Google Scholar
  21. Murata Y, Chiba T, Brundin P, Björklund A, Lindvall O (1990) Formation of synaptic grafthost connections by noradrenergic locus coeruleus neurons transplanted into the adult rat hippocampus. Exp Neurol, submitted.Google Scholar
  22. Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroenceph Clin Neurophysiol 32:281–294Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • J. Bengzon
    • 1
  • M. Kokaia
    • 1
  • P. Brundin
    • 1
  • O. Lindvall
    • 1
  1. 1.Department of Medical Cell ResearchUniversity of LundLundSweden

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