Add-on Effect of Levetiracetam on Cognitive Activity of Carbamazepine and Topiramate Treated Healthy Rats

J Clin Diagn Res. 2015 Jun;9(6):FF01-4. doi: 10.7860/JCDR/2015/12654.6110. Epub 2015 Jun 1.

Abstract

Background: Many antiseizure drugs are used for non-epileptic indications like bipolar disorder, anxiety, neuropathic pain, prophylaxis of migraine, etc. Cognitive problems are known with many of these agents in epileptic situations but not to that extent in other situations. The antiepileptic Levetiracetam has been shown to improve a range of cognitive abilities.

Objective: To study the effect of levetiracetam, carbamazepine, topiramate and co-administration of levetiracetam with carbamazepine and topiramate on cognition in healthy rats.

Materials and methods: Wistar albino rats of either sex were randomly assigned to 6 groups (n=6). Treatment groups: I - Normal saline; II, III & IV- Levetiracetam (180mg/kg), Carbamazepine (50mg/kg) and Topiramate (20mg/kg) respectively; V & VI- Levetiracetam + Carbamazepine and VI- Levetiracetam + Topiramate respectively orally for 21 days. Morris Water Maze was used to study the spatial learning and memory in rats and the change in Escape transfer latency (ETL) was recorded to see the effect of drugs on it. Data analyzed by ANOVA followed by Dunnett's post-hoc test.

Results: Twenty one days drug treatment significantly increased the ETL in rats treated with Topiramate (p=0.0001) and combination of Levetiracetam and Topiramate (p<0.0001) from their baseline values. At the same time, there was significant reduction in the time spent in target quadrant in Topiramate group (p= 0.033) and the combination group of Topiramate + Levetiracetam (p=0.026). No significant change was observed in the other groups when tested for both these parameters.

Conclusion: Topiramate causes impairment of spatial memory in healthy rats after 21 days exposure and its combination with Levetiracetam could not overcome this cognitive deficit.

Keywords: Neuropathic pain; Non-epileptic; Spatial memory.