Effect Of Topiramate On Pentetazole-Induced Epileptic Rats Cognitive Function, Acetylcholine Esterase And Serotonin In Hippocampus.

Objective:To investigate the effects of topiramate on pentetazole-induced epileptic rats cognitive function and the acetylcholine esterase (AChE) activity and the content of serotonin (5-HT) in hippocampus.Methods:60 healthy rats of 4 weeks were randomly divided into 6 groups:blank control group, common dose TPM-control group(TPM A group), large dose TPM control group(TPM B group), PTZ kindled group (PTZ group), common dose TPM-treated group(PTZ+TPM A group), and large dose TPM-treated group(PTZ+TPM B group).Every group had 10 rats. The experiment was started at 8:00 everyday, and the dosage was calculate according to the weight of rats respectively.①The rats in blank group were intragastrically injected 18ml/kg normal saline(NS);②The rats TPM A group were intragastrically injected TPM 18mg/kg(to convert the dose of 200mg/d with adult );③The rats in TPM B group were intragastrically injected TPM 36mg/kg;④The rats in PTZ group were intraperitoneal injected (i.p) PTZ 35mg/kg half hour after intragastrically injected NS 18m1/kg;⑤The rats in PTZ+TPM A group were intragastrically injected TPM 18mg/kg half hour before ip-PTZ 35mg/kg;⑥The rats in PTZ+TPM B group were intragastrically injected TPM 36mg/kg half hour before ip-PTZ 35mg/kg; PTZ and TPM were consecutively used 4 weeks. Every group was subjected to Y-maze to test the learning and memory after the kindled group reaching the criterion of kindling. The activity of AChE in hippocampus was measured by chemicolorimetric method, while the expression of 5-HT in hippocampus by immunohistochemical method.Result:⑴In TPM-control A and B groups, the discrimination learning ability and 24 hours memory retention rate of rats in Y-maze testing were obviously worse (P<0.001), the AChE activity in hippocampus was more higher (P<0.001), and the number of 5-HT positive neuron in immunoreactivity was more smaller (P<0.001) than blank group; compared with TPM-control A group, the discrimination learning ability and 24 hours memory retention rate of rats in Y-maze testing were obviously worse (P<0.001), the AChE activity in hippocampus was higher (P<0.05), and the number of 5-HT positive neuron in immunoreactivity was more smaller (P<0.001) in TPM-control B group;⑵In PTZ kindled group, the discrimination learning ability and 24 hours memory retention rate of rats in Y-maze testing were obviously worse (P<0.001), the AChE activity in hippocampus was more higher (P<0.001), and the number of 5-HT positive neuron in immunoreactivity was more smaller (P<0.001) than blank group;⑶In the TPM-treated A and B groups, the discrimination learning ability and 24 hours memory retention rate of rats in Y-maze testing were obviously better (P<0.001), the AChE activity in hippocampus was more lower (P<0.001) , and the number of 5-HT positive neuron in immunoreactivity was more larger (P<0.001) than PTZ kindled group;⑷In the TPM-treated A group, the discrimination learning ability was obviously better (P<0.001), the 24 hours memory retention rate of rats in Y-maze testing was better (P<0.05), the AChE activity in hippocampus was lower (P<0.05), and the number of 5-HT positive neuron in immunoreactivity was larger (P<0.001) than TPM-control A group; In the TPM-treated B group, the discrimination learning ability was better (P<0.05), the 24 hours memory retention rate of rats in Y-maze testing was better (P<0.01), the AChE activity in hippocampus was lower (P<0.05), and the number of 5-HT positive neuron in immunoreactivity was more larger (P<0.001) than TPM-control B group.Conclusion:⑴TPM was harmful to cognitive function, and the degree of cognitive functional impairment may be related to the does of the drug;⑵The cognitive functional impairment caused by TPM may be concerned with the decrease of 5-HT and the increase of AChE activity in rats hippocampus;⑶The pentylenetetrazol kindled seizures had effect on cognitive function of rats. One of the mechanism could be concerned with the decrease of 5-HT and the increase of AChE activity in rats hippocampus;⑷TPM may indirectly improve cognitive function, by controlling the epilepsy seizure.