| Objective: To investigate the effect of 5-HT1A receptors (8-OH-DPAT)on behavioristics, electrophysiology and neural plasticity in hippocampus of chronic epileptic rats with depression induced by pilocarpine, and to explore the possible pathomechanism of chronic epilepsy with depression.Methods: (1) Animal model: Adult female Sprague-Dawley(SD) rats received pilocarpine intraperitoneally to induce status epilepticus(SE). After 40 minutes, SE was stopped by diazepam and chloral hydrate. The rats in good condition were SE model. The rats receving an injection of normal saline were used as the control group. After 25 days, the rats with depression, selected from the rats with chronic epilepsy, were randomly divided into 4 groups(n=8 each): model, CBZ, CBZ +8- OH-DPAT low dose (0.1mg/kg) and CBZ + 8-OH-DPAT high dose (1.0mg/kg). (2) Behavioral indicators: Recorded the behavioral indicators in epilepsy seizure(intensity and frequency) and depression(weight, appetite, open-field test), and observed the effect of 8-OH-DPAT. (3)Electrophysiology: Recorded the EEG at 3h,25d and 32d after polo kindling. (4) Labeled new neurons with BrdU, then noted pathological changes in the hippocampus with Timm staining. Observed the expression of Nerve growth facto(rNGF)mRNA in the hippocampal dentate gyrus after fluorescence quantitative polymerase chain reaction and the effect of 8-OH-DPAT.Results: (1)Compared with the control group, weight, appetite, squares crossed, rear times and grooming in open-field test in the model group decreased remarkably, while epilepsy seizure intensity, frequency, time of staying in central square and defecation increased significantly(P <0.05). And in the other 3 groups, compared with the model group, weight, appetite, squares crossed, rear times and grooming in open-field test increased remarkably, while epilepsy seizure intensity, frequency, time of staying in central square and defecation decreased significantly(P <0.05). The CBZ + 8-OH-DPAT high dose group, compared with the CBZ group and CBZ + 8-OH-DPAT low dose group, also produced the same results (P <0.05), which had statistical significance. However, the comparing results of the CBZ group and CBZ +8- OH-DPAT low dose group were different, neither of which existed statistical significance. (2)EEG showed accumulated spike waves and short-time latency during acute stage,or epileptic waves and long-time latency during the chronic phase. Compared with the control group, latency in the other 3 groups all prolonged (P <0.001), which had statistical significance. However, the results of the CBZ group and CBZ +8- OH-DPAT low dose group are different, neither of which existed statistical significance. (3)The hippocampal dentate gyrus neurogenesis increased more remarkably in the model group than in the control group (P <0.001), which had statistical significance. And the other 3 groups, compared with the model group, also produced the same results (P <0.001). It also increased more remarkably in the CBZ + 8-OH-DPAT high dose group than in the CBZ group and CBZ + 8-OH-DPAT low dose group (P <0.001), which had statistical significance. However, the results of the CBZ group and CBZ +8- OH-DPAT low dose group were different, neither of which existed statistical significance.(4) The expression of the NGF mRNA and mossy fiber sprouting(MFS)of hippocampal dentate gyrus increased more in the model group than in the other 4 groups (P <0.05). They decreased in the CBZ group and CBZ +8- OH-DPAT low dose group, which had no significant difference. But they decreased more in the CBZ + 8-OH-DPAT high dose group compared with the former 2 groups(P <0.05).Conclusions: (1) The Behavioral indicators and EEG change that antiepileptic treatment is effective. So the animal model is made successfully. The ratio of depression in all chronic epileptic rats is 24%, which proves that coexistence of epilepsy and depression is common in neuropsychiatry. (2) There may be a link among the neurogenesis of hippocampal dentate gyrus, rise of expression of NGFmRNA and MFS. They show that the neuron plasticiy of hippocampus is decreased, which may be one of the pathomechanism of chronic epilepsy with depression. (3) The CBZ + 8-OH-DPAT high dose group benefits the chronic epileptic rats with depression, increases neurogenesis,decreases the expression of NGFmRNA, and MFS, enhances neurogenesis and differentiation of granule cells in the hippocampal dentate gyrus and regulates the neural plasticity of hippocampus,compared with the CBZ group and CBZ +8-OH-DPAT low dose. This may be the mechanism of antiepilepsy with depression by 5-HT1A receptor.
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