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Evaluation of anticonvulsant and nootropic effect of ondansetron in mice
S Jain1, N B Agarwal, P K Mediratta
1Department of Pharmacology, University College of Medical Sciences, University of Delhi, Delhi, India. dr.seemajain@gmail.com
Abstract:
The role of serotonin receptors have been implicated in various types of experimentally induced seizures. Ondansetron is a highly selective 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonist used as antiemetic agent for chemotherapy-, and radiotherapy-induced nausea and vomiting. The present study was carried out to examine the effect of ondansetron on electroshock, pentylenetetrazole (PTZ)-induced seizures and cognitive functions in mice. Ondansetron was administered intraperitoneally (i.p.) at doses of 0.5, 1.0 and 2.0 mg/kg (single dose) to observe its effect on the increasing current electroshock seizure (ICES) test and PTZ-induced seizure test. In addition, a chronic study (21 days) was also performed to assess the effects of ondansetron on electroshock-induced convulsions and cognitive functions. The effect on cognition was assessed by elevated plus maze and passive avoidance paradigms. Phenytoin (25 mg/kg, i.p.) was used as a standard anticonvulsant drug and piracetam (200 mg/kg) was administered as a standard nootropic drug. The results were compared with an acute study, wherein it was found that the administration of ondansetron (1.0 and 2.0 mg/kg) significantly raised the seizure-threshold current as compared to control group in the ICES test. Similar results were observed after chronic administration of ondansetron. In PTZ test, ondansetron in all the three tested doses failed to show protective effect against PTZ-induced seizure test. Administration of ondansetron for 21 days significantly decreased the transfer latency (TL) and prolonged the step-down latency (SDL). The results of present study suggest the anticonvulsant and memory-enhancing effect of ondansetron in mice.
Insights
Ondansetron demonstrated anticonvulsant effects against electroshock seizures and improved cognitive functions in mice. However, it did not protect against pentylenetetrazole-induced seizures, suggesting a specific role in seizure management.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Serotonin receptors are implicated in experimentally induced seizures.
- Ondansetron is a selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, primarily used for nausea and vomiting.
Purpose of the Study:
- To investigate the effects of ondansetron on electroshock and pentylenetetrazole (PTZ)-induced seizures in mice.
- To evaluate the impact of ondansetron on cognitive functions in mice.
Main Methods:
- Ondansetron was administered intraperitoneally at various doses in acute and chronic (21-day) studies.
- Seizure susceptibility was tested using the increasing current electroshock seizure (ICES) and PTZ tests.
- Cognitive functions were assessed using the elevated plus maze and passive avoidance paradigms.
Main Results:
- Ondansetron (1.0 and 2.0 mg/kg) significantly increased the seizure threshold in the ICES test, both acutely and chronically.
- Ondansetron did not provide protection against PTZ-induced seizures at any tested dose.
- Chronic ondansetron administration reduced transfer latency and prolonged step-down latency, indicating memory enhancement.
Conclusions:
- Ondansetron exhibits anticonvulsant properties against electroshock seizures and possesses memory-enhancing effects in mice.
- The drug's efficacy is specific, as it failed to protect against PTZ-induced seizures.
