Psychoneurochemical Investigations to Reveal Neurobiology of Memory Deficit in Epilepsy
Pentylenetetrazole-kindling induced memory deficit has been validated in our previous study. The present study attempts a neurochemical investigation to reveal possible targets for treatment of memory deficit associated with pentylenetetrazole-kindling. Kindling was induced by administering subconvulsive dose of pentylenetetrazole (35 mg/kg; i.p.) at an interval of 48 ± 2 h. Successfully kindled animals were divided into two groups (interictal and postictal group), while non-kindled (naive) animals served as naïve group. In postictal group, animals were challenged with pentylenetetrazole (35 mg/kg) on days 5, 10, 15 and 20. Learning and memory were evaluated in all experimental groups using elevated plus maze and passive shock avoidance paradigm on days 5, 10, 15 and 20. After behavioral evaluations on day 20, all animals were sacrificed to remove their brains. Neurochemical (glutamate, GABA, norepinephrine, dopamine and serotonin) changes and acetylcholinesterase activity and total nitrite level were estimated using HPLC-FD methods and microplate reader method respectively, in discrete brain parts. The results of the neurochemical estimation demonstrated the imbalance in excitatory/inhibitory tone, reduction in monoamine level, elevated nitrosative and acetylcholinesterase activity in the cortex and hippocampus, as responsible factors for the pathobiology of learning and memory deficit in epilepsy. Restoration of these changes may be targeted for the management of memory deficit in epileptic patients.
KeywordsPentylenetetrazole-kindling Epileptic comorbidity Learning and memory deficit Neurotransmitters Post and interictal status
The authors would like to acknowledge the Indian Council of Medical Research, New Delhi, India for the grant of funding for research work and award of Senior Research Fellowship to Mr. Awanish Mishra (Grant No. 45/33/2010/PHA-BMS) and Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala to provide infrastructures and other facilities to carry out research work.
Conflict of interest
The authors declare that they have no conflict of interest related to this manuscript.
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