Effect of carbamazepine and lamotrigine on cognitive function and oxidative stress in brain during chemical epileptogenesis in rats.
The present study assessed the effect of carbamazepine and lamotrigine on cognitive function and oxidative stress in brain during chemically induced epileptogenesis in rats. Epileptogenesis was induced by administration of pentylenetetrazole (30 mg/kg, s.c.) on alternate days (three times/week) for 9-11 weeks or until stage 4 of seizure score was achieved. The neurobehavioural parameters used for cognitive assessment were step-down latency in continuous avoidance apparatus and transfer latency in elevated plus maze test paradigm. Carbamazepine and lamotrigine were administered intraperitoneally in doses of 60 mg/kg and 25 mg/kg, respectively, according to the groups, once a day for 11 weeks. Oxidative stress was assessed in isolated homogenized whole brain samples and estimated for the levels of malondialdehyde, reduced glutathione, catalase and superoxide dismutase. The results showed that lamotrigine did not produce any change in cognitive function, while carbamazepine produced cognitive dysfunction. Cognitive decline seen in the carbamazepine-treated pentylenetetrazole-kindled group was also associated with increased oxidative stress. Lamotrigine treatment had no effect on oxidative stress parameters alone, while it significantly decreased oxidative stress in the pentylenetetrazole-kindled group as compared to the pentylenetetrazole-kindled carbamazepine-treated group.
Arora
Tarun
T
Department of Pharmacology, University College of Medical Sciences, University of Delhi, Delhi, India.
Mehta
Ashish K
AK
Sharma
Krishna K
KK
Mediratta
Pramod K
PK
Banerjee
Basu D
BD
Garg
Gobind R
GR
Sharma
Amit K
AK
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use / Q000633:toxicity*; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002220:Carbamazepine / Q000627:therapeutic use / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced*; D005978:Glutathione / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects; D000077213:Lamotrigine; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D014227:Triazines / Q000627:therapeutic use / Q000633:toxicity*
D000927:Anticonvulsants; D014227:Triazines; D002220:Carbamazepine; D008315:Malondialdehyde; D002374:Catalase; D005978:Glutathione; D000077213:Lamotrigine; D010433:Pentylenetetrazole