Serotonergic modulation of nicotine-induced kinetic tremor in mice
Serotonergic modulation of nicotine-induced kinetic tremor in mice
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尼古丁引起的小鼠动力性震颤的血清素调节
DOI：
10.1016/j.jphs.2017.06.001
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发表时间：
2017
影响因子：
3.5
通讯作者：
Ohno Yukihiro
中科院分区：
文献类型：
--
作者：
Kunisawa Naofumi;Iha Higor A.;Nomura Yuji;Onishi Misaki;Matsubara Nami;Shimizu Saki;Ohno Yukihiro
我们先前证明尼古丁通过α7烟碱型乙酰胆碱(NACH)受体升高下橄榄的神经活动而引起运动性震颤。由于据报道α7 NACH受体促进突触单胺释放，我们探讨了5-羟色胺受体在尼古丁震颤诱导和/或调制中的作用。用尼古丁治疗小鼠引起的运动性震颤，这种震颤通常出现在运动中。5-HT1受体激动剂8-羟基二丙氨基四胺(8-OH-DPAT)可显著增强尼古丁诱发的震颤，其作用可被5-HT1受体拮抗剂Way-100135所拮抗。此外，重复使用对氯苯丙氨酸引起的脑内5-羟色胺的耗竭并没有减少，反而增强了8-OH-DPAT的易化作用。相反，5-HT2激动剂2，5-二甲氧基-4-碘苯丙胺(DOI)可显著减轻尼古丁震颤，其作用可被5-HT2拮抗剂利坦色林所拮抗。5-HT3激动剂SR-57227不影响尼古丁诱发的震颤。此外，在测试5-羟色胺拮抗剂的直接作用时，Way-100135可抑制尼古丁震颤，但不受利坦色林、恩丹西酮(5-HT3拮抗剂)或SB-258585(5-HT6拮抗剂)的影响。这些结果提示，突触后5-HT1A受体参与了α7 NACH受体介导的尼古丁震颤的诱导。此外，5-HT2受体在尼古丁震颤的诱导中具有抑制调节作用。
We previously demonstrated that nicotine elicited kinetic tremor by elevating the neural activity of the inferior olive via α7 nicotinic acetylcholine (nACh) receptors. Since α7 nACh receptors reportedly facilitate synaptic monoamine release, we explored the role of 5-HT receptors in induction and/or modulation of nicotine tremor. Treatment of mice with nicotine induced kinetic tremor that normally appeared during movement. The 5-HT1Aagonist, 8-hydroxydipropylaminotetraline (8-OH-DPAT), significantly enhanced nicotine-induced tremor and the action of 8-OH-DPAT was antagonized by WAY-100135 (5-HT1Aantagonist). In addition, the cerebral 5-HT depletion by repeated treatment with p-chlorophenylalanine did not reduce, but rather potentiated the facilitatory effects of 8-OH-DPAT. In contrast, the 5-HT2agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), significantly attenuated nicotine tremor, which was antagonized by ritanserin (5-HT2antagonist). The 5-HT3agonist SR-57227 did not affect nicotine-induced tremor. Furthermore, when testing the direct actions of 5-HT antagonists, nicotine tremor was inhibited by WAY-100135, but was unaffected by ritanserin, ondansetron (5-HT3antagonist) or SB-258585 (5-HT6antagonist). These results suggest that postsynaptic 5-HT1Areceptors are involved in induction of nicotine tremor mediated by α7 nACh receptors. In addition, 5-HT2receptors have an inhibitory modulatory role in induction of nicotine tremor.