Paper Information

Title:  GRANISETRON LOWERS CLONIC SEIZURE THRESHOLD IN PENTYLENETETRAZOLE INDUCED SEIZURE IN MICE: THE INVOLVEMENT OF NITRIC OXIDE SYSTEM
Type: SPEECH
Author(s): GHOLIPOUR T.,DEHPOUR A.R.
 
 
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2007Volume 18
 
 
Abstract: 

Background: among 7 classes of receptors known for serotonin (5-HT), 5-HT3 is distinct: it is a ligand-dependent cation channel highly permeable to calcium. 5-HT3 receptors are found postsynaptically in GABAergic cortical and limbic neurons beside a variety of other regions. Epileptic seizures can be induced and/or augmented by attenuation of serotonergic neurotransmission. In contrast, manipulations increasing serotonin function (like fluoxetin administration) generally suppress epileptic seizures in animals. Nitric oxide (NO) is found to be either anticonvulsant or proconvulsant in different seizure paradigms. We evaluated the effect of the 5-HT3 antagonist granisetron on clonic seizure induced by pentylenetetrazole (PTZ) and the potential connection with the NO system.
Methods: PTZ (1%) was infused at a constant rate through tail vein catheter of male Swiss mice and minimal dose of PTZ (mg/kg of mice weight) needed to induce clonic seizure was measured as an index of seizure threshold. The interaction of granisetron effects with NO was examined using NO synthase inhibitor L-NAME and substrate L-arginine.
Results: L-NAME could increase seizure threshold in its effective dose (100mg/kg, p<0.01). In other hand, L-arginine showed a proconvulsive effect in doses higher than 100 mg/kg (p<0.01). Mice pretreated with granisetron had lower threshold than controls (31.37 versus 36.95 mg/kg, p<0.01) which could be reversed by effective doses of L-NAME (up to baseline). Co-administration of subeffective doses of granisetron and L-arginine (3 and 75 mg/kg, respectively) demonstrated a synergistic effect (p<0.05).
Conclusion: Our results confirm the proconvulsant role of NO. The NO system involvement is described in the 5-HT3 channel/receptor for the first time. The 5-HT3 receptor antagonist granisetron also showed a proconvulsant effect in this model, probably as a consequence of decreased excitation of GABAergic inhibitory neurons. An anticonvulsive role could be presumed for 5-HT3 agonists.

 
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