Atypical antipsychotics block the excitatory effects of serotonin in septohippocampal neurons in the rat
Atypical antipsychotics block the excitatory effects of serotonin in septohippocampal neurons in the rat
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DOI：
10.1016/s0306-4522(96)00697-5
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发表时间：
1997-07-01
期刊：
影响因子：
3.3
通讯作者：
Alreja, M
中科院分区：
文献类型：
--
作者：
Liu, W;Alreja, M
我们最近报道，5-羟色胺通过多种5-羟色胺受体，包括5-羟色胺(2A)亚型，兴奋大鼠Broca复合体内侧隔/斜角带的GABA能神经元亚群。(1)由于内侧隔/斜角带GABA能神经元的亚群投射到海马区，在本研究中，我们利用细胞外记录检测了5-羟色胺对反向激活的隔海马神经元的影响。沐浴5-羟色胺对大部分隔海马神经元有兴奋作用，平均传导速度为-1.63+/-0.07m/S(n=101)。在药理上，选择性5-羟色胺(2A)拮抗剂MDL 100,907可阻断78%的隔海马神经元5-羟色胺的兴奋作用，其平均pA(2)为8.51+/-0.12(n=22)。此外，非典型抗精神病药物利培酮和氯氮平，而不是典型的抗精神病药物氟哌啶醇，阻断了临床相关浓度的5-羟色胺的兴奋作用。利培酮、氯氮平和氟哌啶醇的pA(2)值分别为8.84+/-0.11、6.57+/-0.13和5.94+/-0.27，给出了效价顺序：利培酮(1.6 nM)、氯氮平(269 NM)和氟哌啶醇(1.1 mM)，与结合研究中报道的结果一致。此外，在全细胞膜片钳记录中，利培酮(10 Nm)阻断了5-羟色胺引起的GABA能突触电流的增加。综上所述，5-羟色胺主要通过5-羟色胺、受体和非典型抗精神病药物在临床相关浓度下阻断这种兴奋。(C)1997年IBRO。爱思唯尔科学有限公司出版。
We recently reported that serotonin excites a subpopulation of GABAergic neurons in the rat medial septum/diagonal band of Broca complex via multiple serotonin receptors, including the serotonin(2A) subtype.(1) Since a subpopulation of medial septum/diagonal band GABAergic neurons projects to the hippocampus, in the present study we tested the effect of serotonin on antidromically-activated septohippocampal neurons using extracellular recordings. Bath-applied serotonin had an excitatory effect in a majority of septohippocampal neurons; serotonin-excited septohippocampal neurons had a mean conduction velocity - 1.63 +/- 0.07 m/s (n=101). Pharmacologically, MDL 100,907, a selective serotonin(2A) antagonist blocked the excitatory effect of serotonin in 78% of septohippocampal neurons tested, with a mean pA(2) of 8.51 +/- 0.12 (n=22). Additionally, the atypical antipsychotics risperidone and clozapine but not the typical antipsychotic haloperidol, blocked the excitatory effects of serotonin at clinically relevant concentrations. The pA(2) values of 8.84 +/- 0.11, 6.57 +/- 0.13 and 5.94 +/- 0.27 for risperidone, clozapine and haloperidol, respectively, obtained in the present study, give a rank order of potency - risperidone (1.6 nM) clozapine (269 nM) haloperidol (1.1 mu M) which corresponds to that reported in binding studies. Additionally, in whole-cell patch-clamp recordings, risperidone (10nM) blocked serotonin-induced increase in GABAergic synaptic currents.In conclusion, serotonin excites septohippocampal neurons primarily via the serotonin,, receptor and atypical antipsychotics block this excitation at clinically relevant concentrations. (C) 1997 IBRO. Published by Elsevier Science Ltd.