Paliperidone increases spontaneous and evoked firing of mesocortical dopaminergic neurons by activating a hyperpolarization-activated inward current
Paliperidone increases spontaneous and evoked firing of mesocortical dopaminergic neurons by activating a hyperpolarization-activated inward current
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帕潘立酮通过激活超极化激活的内向电流来增加中皮质多巴胺能神经元的自发放电和诱发放电
DOI：
10.1016/j.schres.2016.07.003
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发表时间：
2016-10
影响因子：
4.5
通讯作者：
Sun Jinhao
中科院分区：
文献类型：
--
作者：
Dong Haiman;Wang Qian;Zhu Dexiao;Gao Fei;Wang Hui;Bao Lihua;Zhang Jing;Hu Yanlai;Ding Zhaoxi;Sun Jinhao
中皮层多巴胺（DA）能神经元特异性投射到前额皮质，与精神分裂症密切相关。中皮层DA能神经元具有不同于中纹状体和中脑边缘DA能神经元的独特生理特性。帕利哌酮是一种非典型抗精神病药，目前用于治疗精神分裂症，其疗效优于典型抗精神病药。然而，其潜在的生理机制仍不清楚。为了探讨帕利哌酮对中皮层DA神经元活动的影响，在这里，我们用荧光微球逆行标记这些细胞，并在大鼠中脑切片中记录有或没有帕利哌酮的电生理变化。结果表明，帕利哌酮（20 μmol/L）可增加标记的中皮层神经元的自发放电频率（P< 0.05）。此外，帕利哌酮还可增加电流注入刺激诱发动作电位的频率（P< 0.05），而伴随的振幅降低。此外，为了探讨帕潘立酮的作用机制，还检测了Ih电流，结果表明，超极化电压脉冲诱发瞬时Ih电流，帕潘立酮使最大Ih电流增加。此外，帕利哌酮降低自发抑制性突触后电流。因此，帕利哌酮可能通过激活内向电流和减少抑制性突触传递增加中皮层神经元的自发和诱发放电，这提供了帕利哌酮应用于精神分裂症的潜在机制。
Mesocortical dopaminergic (DA) subtype neurons specifically project to the prefrontal cortex, which is closely related with schizophrenia. Mesocortical DA neurons have unique physiological characteristics that are different from those of mesostriatal and mesolimbic DA neurons. Paliperidone, an atypical antipsychotic, is currently used to treat schizophrenia and has better therapeutic effects than typical antipsychotics. However, the underlying physiological mechanism remains unclear. To explore the effects of paliperidone on mesocortical DA neuron activity, here, we retrogradely labeled these cells with fluorescent microsphere retrobeads, and the electrophysiological changes were recorded in whole-cell recordings in rat midbrain slices with or without paliperidone. The data showed that paliperidone (20 μmol/L) increased the spontaneous firing rates of labeled mesocortical neurons (P< 0.05). Moreover, paliperidone also increased the frequency of evoked action potentials by current injection stimulation (P< 0.05), whereas the accompanying amplitude decreased. Furthermore, to explore the mechanisms of paliperidone's effect, Ihcurrents were detected, and the results showed that hyperpolarizing voltage pulses evoked instantaneous Ihinward currents and paliperidone increased the maximum Ihcurrent. In addition, paliperidone decreased the spontaneous inhibitory postsynaptic currents. Thus, paliperidone increased the spontaneous and evoked firing of mesocortical neurons, possibly by activating the Ihinward current and reducing the inhibitory synaptic transmission, which provides an underlying mechanism of paliperidone's application in schizophrenia.
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影响因子：
2.5
作者：
Y. Rateau;N. Ropert
通讯作者：
Y. Rateau;N. Ropert
影响因子：
5.3
作者：
Neuhoff, H;Neu, A;Roeper, J
通讯作者：
Roeper, J
影响因子：
16.2
作者：
Lammel, Stephan;Hetzel, Andrea;Roeper, Jochen
通讯作者：
Roeper, Jochen
影响因子：
2.5
作者：
Zhaoping Liu;E. Bunney;S. B. Appel;M. Brodie
通讯作者：
Zhaoping Liu;E. Bunney;S. B. Appel;M. Brodie
DOI：
10.1124/jpet.111.189076
发表时间：
2012-04-01
影响因子：
3.5
作者：
Muly, E. C.;Votaw, J. R.;Howell, L. L.
通讯作者：
Howell, L. L.