Intestinal inflammation alters the susceptibility to pentylenetetrazole- induced seizure in mice

Kiarash Riazi, Hooman Honar, Houman Homayoun, Shadpour Demehri, Moslem Bahadori, Ahmad Reza Dehpour

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Inflammatory bowel disorders are associated with increased incidence of seizures. Alteration in the endogenous opioid system and overproduction of nitric oxide have been implicated in colitis. The possible contribution of opioid receptors and nitric oxide to increased seizure susceptibility was examined in a putative model of intestinal inflammation. Methods: The alterations in clonic seizure threshold, induced by pentylenetetrazole, following the induction of intestinal inflammation by the administration of two consecutive daily oral doses of croton oil, was evaluated in mice. This model was used to evaluate the effects of pretreatment with opioid receptor antagonist naltrexone (10 mg/kg, once daily for 4 days or a single dose on the test day), non-specific nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (10 mg/kg, once daily), and specific inducible nitric oxide synthase inhibitor aminoguanidine (100 mg/kg, once daily) on seizure threshold in intestinal inflammation. Results: A significant decrease in clonic seizure threshold was observed in mice with intestinal inflammation compared to the control group. Chronic pretreatment with naltrexone per se did not cause any significant change in seizure threshold, but it significantly restored the threshold in croton oil-treated mice to that of the control animals. However, acute naltrexone pretreatment (on the test day) could not restore the decreased seizure threshold to control level. Chronic pretreatment with neither NG-nitro-L-arginine methyl ester nor aminoguanidine altered the seizure threshold in the control animals and in mice treated with croton oil. Conclusions: Experimental croton oil-induced intestinal inflammation leads to a proconvulsant effect, which may have clinical relevance. Chronic alterations mediated by endogenous opioids may be involved in this process, though a direct opioid-receptor-mediated effect is unlikely. Nitric oxide synthesis, via constitutive or inducible pathways, is not involved in this increased susceptibility.

Original languageEnglish (US)
Pages (from-to)270-277
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume19
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

Keywords

  • Clonic seizure threshold
  • Intestinal inflammation
  • Mice
  • Nitric oxide
  • Opioid receptors
  • Pentylenetetrazole

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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