Evidence for increased dorsal hippocampal adenosine release and metabolism during pharmacologically induced seizures in rats

Robert F Berman, Bertil B. Fredholm, Ulrika Aden, William T. O'Connor

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Abstract

There is growing pharmacological evidence from several animal models of seizure disorder that adenosine possesses endogenous anticonvulsant activity. In order to further evaluate the role of adenosine in seizure activity, we monitored adenosine and its major biochemical metabolites inosine, xanthine, and hypoxanthine in the dorsal hippocampus by in vivo microdialysis before and during the induction of generalized seizures. Seizures were induced pharmacologically in groups of urethane-anesthetized rats by the administration of bicuculline (0.5 mg/kg, i.v.), kainic acid (12.0 mg/kg, i.v.) or pentylenetetrazol (100-250 mg/kg, i.p). Seizure activity was monitored electrophysiologically from the dorsal hippocampus. Dialysate hippocampal purine levels increased during all three seizure types. The largest increases were for the adenosine metabolites hypoxanthine and inosine, with smaller increases observed for adenosine and xanthine. Intra- hippocampal perfusion with the adenosine deaminase inhibitor erythro-9-(2- hydroxy-3-nonyl-adenine, (EHNA, 300 μM), only slightly increased basal hippocampal adenosine. Guanosine levels in the hippocampus, a purine not directly related to adenosine metabolism, were unaffected by all treatments. These findings demonstrate that an increase in hippocampal adenosine release and metabolism is associated with seizure activity and support the hypothesis that the increased adenosine levels may attenuate hippocampal seizure activity, possibly by terminating ongoing seizures and altering the pattern of subsequent seizures. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)44-53
Number of pages10
JournalBrain Research
Volume872
Issue number1-2
DOIs
StatePublished - Jul 28 2000

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Keywords

  • Adenosine
  • Adenosine deaminase
  • Bicuculline
  • Epilepsy
  • Hippocampus
  • Hypoxanthine
  • Inosine
  • Ka inate
  • Microdialysis
  • Pentylenetetrazol
  • Xanthine

ASJC Scopus subject areas

  • Neuroscience(all)

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