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Effect of Lamotrigine, Levetiracetam and Phenytoin on Learning and Memory in Albino Rats


Affiliations
1 Pharmacology AIIMS, New Delhi, India
2 Pharmacology of Therapeutics RIMS, Ranchi, India
 

Background: Epilepsy is one of the most prevalent non-communicable neurologic diseases leading to significant disability and mortality. Complaints of impaired learning and memory are common in patients of epilepsy. Antiepileptic drugs (AEDs) may further enhance this impairment. So the present study was carried out on albino rats to evaluate the effect of AEDs on learning and memory.

Objective: To assess the effect of lamotrigine, levetiracetam and phenytoin on learning and memory in albino rats.

Material and Methods: Albino rats of about 150 -200 gm of either sex were treated with drugs for 15 days and assessed for effect on learning behavior and again treated for next 15 days after which they were assessed for retention behavior (memory) on Morris water maze and Elevated plus maze. The data was statistically analyzed by applying Mann- Whitney test.

Result:Phenytoin and lamotrigine caused significant impairment of learning whereas levetiracetam had no statistically significant effect on learning. Phenytoin also caused significant impairment of memory whereas lamotrigine and levetiracetam did not cause statistically significant impairment of memory.

Conclusion: Learning was impaired by phenytoin and lamotrigine but not by levetiracetam which has novel mechanism of action. Phenytoin resulted in memory impairment on Morris water maze but no impairment on elevated plus maze and no other drug caused this effect.


Keywords

Anti Epileptic Drugs, Learning, Memory, Elevated Plus Maze, Morris Water Maze.
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  • Ngugi AK, Bottomley C, Kleinschmidt I. Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia 2010;51(5):883-90.

  • Shannon HE. Cognitive Effects of Antiepileptic Drugs, In: Steven C Schachter, Gregory L Homes, Dorothee kasteleijin-Nolst Trenite, editors. Behavioral Aspect of Epilepsy: Principal and Practice. 1st edition. New York: Demos Medical Publishing; 2008.p. 43.

  • Brunbech L, Sabers A. Effect of antiepileptic drugs on cognitive function in individuals with epilepsy: a comparative review of newer versus older agents. Drugs 2002;62(4):593-604.

  • Smith DB, Mattson RH, Cramer JA, Collins JF, Novelly RA. Results of a nationwide Veterans Administration Cooperative Study comparing the efficacy and toxicity of carbamazepine, phenobarbital, phenytoin, and primidone. Epilepsia 1987;28:S50-8.

  • Martin R, Kuzniecky R, Ho S, Hetherington H, Pan J, Sinclair K, et al. Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology1999;52:321–7.

  • Bootsma HP, Aldenkamp AP, Diepman L, Hulsman J, Lamnrechts D, Leenan L, et al. The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice, Epilepsia 2006;47:24-7.

  • Gomer B, Wagner K, Frings L, Sar J, Carius A, Harle M, et al. The influence of antiepileptic drugs on cognition: a comparison of levetiracetam with topiramate. Epilepsy Behav 2007; 10(3):486-94.

  • Daniel H Lowenstein. Seizure and Epilepsy. In: Fauci AS, Braunwald EB, Kasper DL, Stepen L Hauser, Dan L Longo, J Larry Jameson, Joseph Loscalzo, editors. Harrison’s Principle of Internal Medicine. 17th edition. New York: Mc Graw Hill; 2008.p. 2507.

  • D Hooge R, De Deyn PP. Applications of the Morris water maze in the study of learning and memory. Brain Research Reviews 2001;36:60-90.

  • Itoh J, Nabeshima T, Kameyama T, Utility of an elevated plus-maze for the evaluation of memory in mice: effects of nootropics, scopolamine and electroconvulsive shock. Psychopharmacology (Berl) 1990;101 (1):27-33.

  • Sharma AC, Kulkarni SK. Evaluation of learning and memory mechanisms employing elevated plus-maze in rats and mice. Progress in Neuro- Psychopharmacology and Biological Psychiatry 1992;16:117-125.

  • Akaho R. The effects of antiepileptic drugs on cognition in normal volunteers. Psychiatry Clin Neurosci 1996;50(2):619.

  • Banks MK, Mohr NL, Besheer J, Steinmetz JE, Garraghty PE. The effects of phenytoin on instrumental appetitive to aversive transfer in rats. Pharmacol Biochem Behav 1999;63(3):465-72.

  • Besheer J, Holloway JL, Banks MK, Phipps E, Garraghty PE. The effects on learnimg of phenytoin in adult rats exposed to the drug during development. Neuroscience Abstracts 1997;23:2166.

  • Mecarelli O, Vicenzini E, Pulitano P, Vanacore N, Romolo FS, Di Piero V, et al. Clinical, cognitive, an neurophysiologic correlates of short-term treatment with carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers. Ann Pharmacother 2004;38:1816–22.

  • Neyens LGJ, Alpherts WCJ, Aldenkamp AP. Cognitive effects of a new pyrrolidine derivative (levetiracetam) in patients with epilepsy. Prog NeuroPsychopharmacol Biol Psychiatry 1995;19:411–9.

  • Cramer JA, Arrigo C, Van Hammee G, Gauer LJ, Cereghino JJ. Effect of levetiracetam on epilepsy-related quality of life. Epilepsia 2000;41:868–74.

  • Pressler RM, Binnier CD, Coleshill SG, Chorley SG, Robinson RO. Effect of lamotrigine on cognition in children with epilepsy. Neurology 2006;66:1495–9.


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  • Effect of Lamotrigine, Levetiracetam and Phenytoin on Learning and Memory in Albino Rats

Abstract Views: 238  |  PDF Views: 166

Authors

Subodh Kumar
Pharmacology AIIMS, New Delhi, India
Harmanjit Singh
Pharmacology AIIMS, New Delhi, India
Janardan Sharma
Pharmacology of Therapeutics RIMS, Ranchi, India

Abstract


Background: Epilepsy is one of the most prevalent non-communicable neurologic diseases leading to significant disability and mortality. Complaints of impaired learning and memory are common in patients of epilepsy. Antiepileptic drugs (AEDs) may further enhance this impairment. So the present study was carried out on albino rats to evaluate the effect of AEDs on learning and memory.

Objective: To assess the effect of lamotrigine, levetiracetam and phenytoin on learning and memory in albino rats.

Material and Methods: Albino rats of about 150 -200 gm of either sex were treated with drugs for 15 days and assessed for effect on learning behavior and again treated for next 15 days after which they were assessed for retention behavior (memory) on Morris water maze and Elevated plus maze. The data was statistically analyzed by applying Mann- Whitney test.

Result:Phenytoin and lamotrigine caused significant impairment of learning whereas levetiracetam had no statistically significant effect on learning. Phenytoin also caused significant impairment of memory whereas lamotrigine and levetiracetam did not cause statistically significant impairment of memory.

Conclusion: Learning was impaired by phenytoin and lamotrigine but not by levetiracetam which has novel mechanism of action. Phenytoin resulted in memory impairment on Morris water maze but no impairment on elevated plus maze and no other drug caused this effect.


Keywords


Anti Epileptic Drugs, Learning, Memory, Elevated Plus Maze, Morris Water Maze.

References





DOI: https://doi.org/10.18311/ijmds%2F2014%2F81260