Synergistic neurochemical and behavioural effects of acute intrahippocampal injection of brain-derived neurotrophic factor and antidepressants in adult mice
Synergistic neurochemical and behavioural effects of acute intrahippocampal injection of brain-derived neurotrophic factor and antidepressants in adult mice
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DOI：
10.1017/s1461145709000017
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发表时间：
2009-08-01
影响因子：
4.8
通讯作者：
Gardier, Alain M.
中科院分区：
文献类型：
--
作者：
Deltheil, Thierry;Tanaka, Kenji;Gardier, Alain M.
临床前数据支持以下观点：脑衍生的神经营养因子（BDNF）和血清素能系统调节参与情感障碍的电路。本研究检查了BDNF的急性汉皮门内注射BDNF的神经化学和行为后果与抗抑郁药结合使用，通过使用体内脑内微透析在腹侧海马（VHI）（VHI）中，在有意识的小鼠和行为态度中预测了抗抗抑阻度和对抗焦点的抗气效应（抗焦点 - 抗抗气状态）。 （OF）范式和高架Plus迷宫（EPM）]。神经化学数据表明，BDNF（100 ng）增强了5-羟色胺选择性再摄取抑制剂（SSRI; Paroxetine 4 mg/kg I.P.）的影响，并在VHI中透析5-HT水平上的局部施用的西氧甲威普兰灌注。这些神经化学变化与行为数据相关，因为在FST中，BDNF增强了帕罗西汀的抗抑郁样活性。这些数据表明BDNF和SSRI在抗抑郁药样活性上具有有趣的协同作用。此外，在OF和EPM范式中，BDNF都诱导了焦虑样活性，而帕罗西汀则阻止了这种作用。最后，BDNF对血清素能系统的神经化学和行为影响可能在突触前和突触后水平上都发生，因为通过使用原位杂交，我们表明TRKB-R mRNA在海马体和成年小鼠中的背部raphe核中表达。总而言之，BDNF的神经化学和行为效应表明，这些行为变化是通过VHI 5-HT神经传递的增加来介导的。因此，BDNF + SSRI组合可以提供治疗情绪障碍的新替代方法。
Preclinical data support the view that brain-derived neurotrophic factor (BDNF) and serotonergic systems regulate circuits involved in affective disorders. The present study examined neurochemical and behavioural consequences of an acute intrahippocampal injection of BDNF combined with an antidepressant by using in-vivo intracerebral microdialysis in the ventral hippocampus (vHi) in conscious mice and behavioural paradigms predictive of antidepressant and anxiolytic-like effects [the mouse forced swim test (FST), the open-field (OF) paradigm and the elevated plus maze (EPM)]. Neurochemical data revealed that BDNF (100 ng) potentiated the effects of the systemic administration of a serotonin selective reuptake inhibitor (SSRI; paroxetine 4 mg/kg i.p.) and that of a locally applied citalopram perfusion on dialysate 5-HT levels in the vHi. These neurochemical changes correlated with behavioural data since, in the FST, antidepressant-like activity of paroxetine as measured on swimming behaviour was potentiated by BDNF. These data suggest an interesting synergy between BDNF and SSRI on antidepressant-like activity. Furthermore, in both the OF and EPM paradigms BDNF induced an anxiogenic-like activity, whereas paroxetine prevented this effect. Finally, the neurochemical and behavioural effects of BDNF on the serotonergic system might occur at both pre- and post-synaptic levels since by using in-situ hybridization, we showed that TrkB-R mRNA was expressed in the hippocampus and the dorsal raphe nucleus in adult mice. Taken together the neurochemical and behavioural effects of BDNF suggest that these behavioural changes were mediated by increases in 5-HT neurotransmission in vHi. Thus a BDNF + SSRI combination may offer new alternatives to treat mood disorders.