Comparative behavioral and neurochemical analysis of phenytoin and valproate treatment on epilepsy induced learning and memory deficit: Search for add on therapy

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• 作者：Awanish Mishra ; Rajesh Kumar Goel
• 关键词：Pentylenetetrazole ; kindling ; Learning and memory deficit ; Epileptic comorbidity ; antiepileptic drugs ; Phenytoin ; Sodium valproate
• 刊名：Metabolic Brain Disease
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：30
• 期：4
• 页码：951-958
• 全文大小：659 KB
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• 作者单位：Awanish Mishra (1)
  Rajesh Kumar Goel (1)
  
  1. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, Punjab, India
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Neurosciences
  Neurology
  Biochemistry
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7365

文摘

Our previous work demonstrated, chronic epilepsy affects learning and memory of rodents along with peculiar neurochemical changes in discrete brain parts. Most commonly used antiepileptic drugs (phenytoin and sodium valproate) also worsen learning and memory in the patients with epilepsy. Therefore this study was designed to carry out comparison of behavioral and neurochemical changes with phenytoin and sodium valproate treatment in pentylenetetrazole-kindling induced learning and memory deficit to devise add on therapy for this menace. For the experimental epilepsy, animals were kindled using PTZ (35?mg/kg; i.p., at 48?±-?h intervals) and successful kindled animals were involved in the study. These kindled animals were treated with saline, phenytoin (30?mg/kg/day, i.p.) and sodium valproate (300?mg/kg/day, i.p.) for 20?days. These animals were challenged with PTZ challenging dose (35?mg/kg) on day 5, 10, 15 and 20 to evaluate the effect on seizure severity score on different days. Effect on learning and memory was evaluated using elevated plus maze and passive shock avoidance paradigm. On day 20, after behavioral evaluations, animals were sacrificed to analyze glutamate, GABA, norepinephrine, dopamine, serotonin, total nitrite level and acetylcholinesterase level in cortex and hippocampus. Behavioral evaluations suggested that phenytoin and sodium valproate treatment significantly reduced seizure severity in the kindled animals, while sodium valproate treatment controls seizures with least memory deficit in comparison to phenytoin. Neurochemical findings revealed that elevated cortical acetylcholinesterase level could be one of the responsible factors leading to memory deficit in phenytoin treated animals. However sodium valproate treatment reduced cortical acetylcholinesterase level and had least debilitating consequences on memory deficit. Therefore, attenuation of elevated AChE activity can be one of add-on approach for management of memory deficit associated with conventional AEDs.