氯氮平对家兔海马齿状回突触传递及神经递质释放的影响

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (5): 490-495.

氯氮平对家兔海马齿状回突触传递及神经递质释放的影响

王曼¹, 马慧², 地引逸龟³, 窐田孝³, 石川晓³, 川村友美³

¹中国医科大学第一医院精神医学科,沈阳 110001,辽宁;
²燕山大学心理健康服务中心,秦皇岛 066000,河北;
³日本金泽医科大学精神医学科,河北郡 920-0293,石川县

收稿日期:2010-04-08 修回日期:2010-05-05 出版日期:2010-05-26 发布日期:2020-09-16
作者简介:王曼,女,博士在读,主治医师,研究方向:精神药理学。Tel: 024-83282184 E-mail: wangman1976@126.com

Effects of clozapine on the synaptic transmission and extracellular neurotransmitters release in the hippocampus of rabbits

WANG Man¹, MA Hui², Jibiki Itsuki³, Kubota Takashi³, Ishikawa Akira³, Kawamura Tomomi³

¹Department of Psychiatry, the First Hospital of China Medical University, Shenyang 110001, Liaoning, China;
²Center of Mental Health Service, Yan Shan University, Qinhuangdao 066000, Hebei, China;
³Department of Neuropsychiatry, Kanazawa Medical University, 920-0293, Japan

Received:2010-04-08 Revised:2010-05-05 Online:2010-05-26 Published:2020-09-16

摘要/Abstract

摘要： 目的: 观察给予氯氮平前后齿状回反应及细胞外多巴胺(DA)和5-羟色胺(5-HT)水平的变化规律。方法: 15只成年家兔,将刺激用微电极置于海马穿通纤维处,记录用微电极和收集神经递质的引导插管置于同侧齿状回处,经 10 d 康复后随机分为对照组(C组)、强直刺激组(T组)和无强直刺激组(N组),每组各5只。整个实验 180 min,分3阶段(60 min/阶段)。全程给予齿状回单极方脉冲电刺激,60 min 时分别腹腔注射 20 mg/kg 氯氮平溶液(T组和N组)或空白溶剂(C组),120 min 时给予强直刺激(C组和T组)。实验中,每隔 2 min 记录一次齿状回反应,每隔 5 min 检测一次齿状回细胞外DA和5-HT的水平。结果: 齿状回反应:C组1、2阶段无改变(P＞0.05),3阶段较1、2阶段增强(P＝0.02),产生长时程增强(LTP);T组2阶段较1阶段增强(氯氮平增强)(P＝0.004), 3阶段较2阶段进一步增强(P＝0.02),产生LTP;N组2阶段较1阶段增强(氯氮平增强)(P＝0.004), 3阶段同2阶段(P＞0.05)。细胞外DA和5-HT的水平:C组的DA水平在3个阶段均无改变(P＞0.05);T组2、3阶段DA水平较1阶段明显升高(P＜0.01),但3阶段的DA水平却没有因LTP的产生而出现相应的改变; N组2、3阶段DA水平较1阶段明显升高(P＜0.01);3组在全部实验中的5-HT水平均无改变(P＞0.05)。结论: 氯氮平可在齿状回同步产生氯氮平增强和细胞外DA水平的增加。

关键词: 氯氮平增强, 多巴胺, 5-羟色胺, 长时程增强

Abstract: AIM: To observe whether clozapine can alter the synaptic transmission and extracellular neurotransmitters release in the hippocampus of rabbits. METHODS: The stimulating microelectrodes were inserted into the perforant path of hippocampus in 15 rabbits, while the recording microelectrodes and guide cannulas were inserted into homolateral dentate gyrus of the rabbits. After a 10-day recovery period, they were divided into three groups randomly (n=5): contral(C) group, tetanic stimulation (T) group and without tetanic stimulation (N) group. There were 3 sessions (60 mins/session) in the total 180 mins. Every rabbit was given single stimuli at a fixed intensity(monopolar square pulse of 0.2 ms duration, 200-300 μA,30-second stimulus intervals) in dentate gyrus. T and N were intraperitoneally injected with clozapine resolution(20 mg/kg) and C were intraperitoneally injected with blank solvent after 60 min, while C and T were given a titanic stimulation after 120 min. The synaptic responses in dentate gyrus were recorded every 2 min, and the microdialysis samples were collected to examine the extracellular DA and 5-HT levels every 5 min. RESULTS: The response in dentate gyrus: there was clozapine-induced potentiation in group T and N in session 2(P＝0.004), and there was LTP in group T and C in session 3(P＝0.02). The extracellular DA and 5-HT levels: DA levels were increased significantly in group T in session 2 and 3 when compared with session 1(ther was not responding change of DA levels in session 3)(P＜0.01), DA levels were increased significantly in group N after clozapine administration(P＜0.01), while DA levels in group C and the levels of 5-HT in 3 groups were not changed(P＞0.05). CONCLUSION: Clozapine almost affect the excitatory synaptic response and extracellular DA levels in hippocampus simultaneously.

Key words: Clozapine-induced potentiation, Dopamine, Serotonin, Long-term potentiation

中图分类号:

R965.2

王曼, 马慧, 地引逸龟, 窐田孝, 石川晓, 川村友美. 氯氮平对家兔海马齿状回突触传递及神经递质释放的影响[J]. 中国临床药理学与治疗学, 2010, 15(5): 490-495.

WANG Man, MA Hui, Jibiki Itsuki, Kubota Takashi, Ishikawa Akira, Kawamura Tomomi. Effects of clozapine on the synaptic transmission and extracellular neurotransmitters release in the hippocampus of rabbits[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(5): 490-495.

参考文献

[1] Kubota T, Jibiki I, Kishizawa S, et al. Clozapine-induced potentitation of synaptic response in the perforant path-dentate gyrus pathway in chronically prepared rabbits[J]. Neurosci Lett,1996,211(1):21-24.
[2] Kubota T, Jibiki I, Kurokawa S. Effects of zetapine on excitatory synaptic response in the perforant path-dentate gyrus pathway in chronically prepared rabbits[J]. Eur J Pharmacol, 2002,453 (2/3):245-250.
[3] Kubota T, Jibiki I, Enokido F, et al. Effects of MK-801 on clozapine-induced potentitation of excitatory synaptic response in the perforant path-dentate gyrus pathway in chronically prepared rabbits[J]. Eur J Pharmacol, 2000,395(1):37-42.
[4] Chung YC, Li Z, Dai J, et al. Clozapine increases both acetylcholine and dopamine release in rat ventral hippocampus: role of 5-HT1A receptor agonist[J]. Brain Res, 2004,1023(1):54-63.
[5] Chen L, Yang CR. Interaction of dopamine D1 and NMDA receptor mediates acute clozapine potentiation of glutamate EPSPs in rat prefrontal cortex[J]. J Neurophysiol, 2002,87(5):2324-2336.
[6] Ichikawa J, Li Z, Dai J, et al. Atypical antipsychotic drugs, quetiapine, iloperidone, and meloperone, preferentially increases dopamine and acetylcholine release in rat medial prefrontal cortex[J]. Brain Res, 2002,956(2): 349-357.
[7] Melone M, Vitellaro-Zuccarello L, Vallejo-Illarramendi A, et al. The expression of glutamate transporter GLT-1 in the rat cerebral cortex is down-regulated by the antipsychotic drug clozapine[J]. Mol Psychiatry, 2001,6(4):380-386.
[8] Mrzljak L, Bergson C, Pappy M, et al. Localization of dopamine D4 receptors in GABAergic neurons of the primate brain[J]. Nature, 1996,381(6579):245-248.
[9] Assie MB, Ravailhe V, Faucillon V, et al. Contrasting contribution of 5-hydroxytryptamine 1A receptor activation to neurochemical profile of novel antipsychotics: frontal dopamine and hippocampal serotonin release in rat brain[J]. J Pharmacol Exp Ther,2005,315(1):265-272.
[10] Matsumoto M, Shikanai H, Togashi H, et al. Characterization of clozapine-induced changes in synaptic plasticity in the hippocampal-mPFC pathway of anesthetized rats[J]. Brain Res, 2008,1195(1):50-55.

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