5-HT1B受体亚型对小脑顶核介导的运动行为的影响

doi:10.13459/j.cnki.cjap.2016.06.014

摘要/Abstract

摘要： 目的：探讨5-羟色胺（5-HT）能神经系统在经小脑顶核介导的运动行为中的作用。方法：采用大鼠离体脑片膜片钳及大鼠走步机的行为学测试方法。结果：阻断5-HT_1B受体能够增强小脑顶核兴奋性突触传递，行为学试验中给予5-HT及5-HT_1B受体阻断剂SB224289，发现注射5-HT到小脑顶核后，大鼠在Rota-rod走步机上的持续时间显著延长，而给予其阻断剂SB224289后，能够反转此作用。结论：5-HT很可能通过5-HT_1B受体抑制顶核神经元的兴奋性突触传递从而调节小脑核团神经元环路的活动，继而影响小脑的最终输出，实现对小脑顶核介导的运动平衡和协调能力的调控。

关键词: 5-HT, 5-HT_1B受体, 小脑顶核, 兴奋性突触后电流, 大鼠, 膜片钳

Abstract: Objective: To investigate the effects of the serotonergic nervous system on motor behaviors mediated by cerebellar fastigial nucleus (FN). Methods: In this experiment, the main methods are whole-cell patch clamp recording and Rota-rod test. Results: We found that the excitatory synaptic transmission was enhanced in the cerebella FN after blocking 5-hydroxytryptamine,(5-HT)receptor. Microinjection of 5-HT into FNs remarkably promoted motor performances on Rota-rod, which could be reversed by microinjection of 5-HT receptor antagonist SB224289. Conclusion: These results suggest that the 5-HT can suppress cerebellar FN excitatory synaptic transmission via 5-HT_1B receptors, thereby modulate the activity of cerebellar nuclear neurons circuitry, and subsequently influence the cerebellum-mediated ongoing motor balance and coordination.

Key words: 5-HT, 5-HT_1B receptor, fastigial nucleus (FN), excitatory post-synaptic currents, rat, patch clamp

中图分类号:

高伟, 王楠, 乔虎. 5-HT_1B受体亚型对小脑顶核介导的运动行为的影响[J]. 中国应用生理学杂志, 2016, 32(6): 550-554.

GAO Wei, WANG Nan, QIAO Hu. The effects of 5-HT_1B receptor subtypes on motor behaviors mediated by cerebellar fastigial nucleus[J]. CJAP, 2016, 32(6): 550-554.

参考文献

[1] Ito M. The modifiable neuronal network of the cerebellum[J]. Jpn J Physiol, 1984, 34(5):781-792.
[2] 杨东升, 刘晓莉, 乔德才. 力竭运动及恢复期大鼠纹状体5-HT、DA及其代谢物浓度的动态变化研究[J]. 中国应用生理学杂志, 2011, 27(4):432-436.
[3] 张健, 胡旺平, 周克纯, 等. 5-HT2和5-HT3受体在外周初级感觉神经末梢痛反应和痛调制中的相互作用[J]. 中国应用生理学杂志, 2006, 22(1):40-44.
[4] 刘洪珍, 曾莉, 孔喜良, 等. 复方中药对大鼠力竭运动与恢复过程中端脑神经递质含量的影响[J]. 中国应用生理学杂志, 2011, 27(4):439-443.
[5] Schweighofer N, Doya K, Kuroda S. Cerebellar aminergic-neuromodulation:towards a functional understanding[J]. Brain Res Brain Res Rev, 2004, 44(2-3):103-116.
[6] Mori S, Matsui T, Kuze B, et al. Stimulation of a restricted region in the midline cerebellar white matter evokes coordi-nated quadrupedal locomotion in the decerebrate cat[J]. J Neurophysiol, 1999, 82(1):290-300.
[7] Sari Y. Serotonin1B receptors:from protein to physiological fu nction and behavior[J]. Neurosci Biobehav Rev, 2004, 28(6):565-82.
[8] Griebel G, Saffroy-Spittler M, Misslin R, et al. Serenics-fluprazine (DU 27716) and eltoprazine (DU 28853) enhance neophobic and emotional behaviour in mice[J]. Psychophar-macology (Berl), 1990, 102(4):498-502.
[9] Boulenguez P, Foreman N, Chauveau, et al. Distractibility and locomotor activity in rat following intra-collicular injec-tion of a serotonin 1B-1D agonist[J]. Behav Brain Res, 1995, 67(2):229-239.
[10] Song YN, Li HZ, Zhu JN, et al. Histamine improves rat rots-rod and balance beam performances through H(2) re-ceptors in the cerebellar interpositus nucleus[J]. Neurosci, 2006, 140(1):33-43.
[11] He YC, Wu GY, Li D, et al. Histamine promotes rat motor performances by activation of H(2) receptors in the cerebel-lar fastigial nucleus[J]. Behav Brain Res, 2012, 228(1):44-52.
[12] Yew DT, Yeung LY, Wai MS, et al. 5-HT 1A and 2A re-ceptor positive cells in the cerebella of mice and human and their decline during aging[J]. Microsc Res Tech, 2009, 72(9):684-689.
[13] Choi DS, Maroteaux L. Immunohistochemicallocalisation of the serotonin 5-HT2B receptor in mouse gut, cardiovascular system, and brain[J]. FEBS Lett, 1996, 391(1-2):45-51.
[14] Gérard C, el Mestikawy S, LebrandC, et al. Quantitative RT-PCR distribution of serotonin 5-HT6 receptor mRNA in the central nervous system of control or 5, 7-dihydrox-ytryptamine-treated rats[J]. Synapse, 1996, 23(3):164-173.
[15] Geurts FJ, De Schutter E, Timmermans JP. Localization of 5-HT2A, 5-HT3, 5-HT5A and 5-HT7 receptor-like im-munoreactivity in the rat cerebellum[J]. Neuroanat, 2002, 24(1):65-74.
[16] Boschert U, Amara DA, SeguL, et al. The mouse 5-hydrox-ytryptamine1B receptor is localized predominantly on axon terminals[J]. Neurosci, 1994, 58(1):167-182.
[17] Sari Y, Miquel MC, Brisorgueil MJ, et al. Cellular and subcellular localization of 5-hydroxytryptamine1B receptors in the rat central nervous system:immunocytochemical, autora-diographic and lesion studies[J]. Neurosci, 1999, 88(3):899-915.
[18] Murano M, Saitow F, Suzuki H. Modulatory effects of sero-tonin on glutamatergic synaptic transmission and long-term depression in the deep cerebellar nuclei[J]. Neurosci, 2011, 172:118-128.
[19] Singer JH, Bellingham MC, Berger AJ. Presynaptic inhibi-tion of glutamatergic synaptic transmission to rat motoneurons by serotonin[J]. J Neurophysiol, 1996, 76(2):799-807.
[20] Shen KZ, Johnson SW. 5-HT inhibits synaptic transmission in rat subthalamic nucleus neurons in vitro[J]. Neurosci, 2008, 151(4):1029-1033.
[21] De Souza RJ, Goodwin GM, Green AR, et al. Effect of chronic treatment with 5-HT1 agonist (8-OH-DPAT and RU 24969) and antagonist (isapirone) drugs on the behavioural responses of mice to 5-HT1 and 5-HT2 agonists[J]. Br J Pharmacol, 1986, 89(2):377-384.
[22] Green AR, Guy AP, Gardner CR. The behavioural effects of RU 24969, a suggested 5-HT1 receptor agonist in rodents and the effect on the behaviour of treatment with antidepres-sants[J]. Neuropharmacol, 1984, 23(6):655-661.
[23] Kalueff AV, Jensen CL, Murphy DL. Locomotory patterns, spatiotemporal organization of exploration and spatial memory in serotonin transporter knockout mice[J]. Brain Res, 2007, 1169:87-97.