Comparison of ΔFosB Immunoreactivity Induced by Vagal Nerve Stimulation with That Caused by Pharmacologically Diverse Antidepressants
Comparison of ΔFosB Immunoreactivity Induced by Vagal Nerve Stimulation with That Caused by Pharmacologically Diverse Antidepressants
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DOI：
10.1124/jpet.111.188953
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发表时间：
2012-05-01
影响因子：
3.5
通讯作者：
Frazer, Alan
中科院分区：
文献类型：
--
作者：
Furmaga, Havan;Sadhu, Mohona;Frazer, Alan
迷走神经刺激（VNS）已被批准用于治疗难治性抑郁症。然而，很少有（如果有的话）直接比较VNS在动物中产生的效果与抗抑郁药引起的效果的研究，特别是在非麻醉动物中使用临床相关的刺激参数。在这项研究中，Delta FosB免疫组化被用来评估不同的大脑区域激活的长期管理的VNS。并与舍曲林或地昔帕明（舍曲林、地昔帕明）进行比较。用DeltaFosB和5-羟色胺双标记法观察长时程迷走神经刺激是否激活中缝背核（DRN）内的多巴胺能神经元。VNS显着增加Delta FosB染色在孤束核（NTS），臂旁核（PBN），蓝斑（LC），和DRN，以及在许多皮质和边缘系统的大脑区域，包括那些参与情绪和认知。大部分，但不是全部，这些影响也被认为是长期治疗的大鼠舍曲林或顺铂。VNS增加Delta FosB的一些地区（e。例如，在一个实施例中，NTS、PBN、LC和脚周核）不受任一药物的显著影响。舍曲林在引起DRN增加方面与VNS相似，而DMI则不然。用Delta FosB和5-羟色胺抗体对DRN进行双标记，发现DRN中只有一小部分Delta FosB染色与多巴胺能神经元共定位。VNS的影响比抗抑郁药引起的影响更广泛。VNS产生的Delta FosB的增加与抗抑郁药相当和/或比抗抑郁药更强。
Vagal nerve stimulation (VNS) has been approved for treatment of refractory depression. However, there have been few, if any, studies directly comparing the effects produced by VNS in animals with those caused by antidepressants, particularly using clinically relevant stimulation parameters in nonanesthetized animals. In this study, Delta FosB immunohistochemistry was used to evaluate different brain regions activated by long-term administration of VNS. Effects of VNS were compared with those caused by sertraline or desipramine (DMI). Double-labeling of Delta FosB and serotonin was used to determine whether serotonergic neurons in the dorsal raphe nucleus (DRN) were activated by long-term VNS. VNS significantly increased Delta FosB staining in the nucleus tractus solitarius (NTS), parabrachial nucleus (PBN), locus ceruleus (LC), and DRN, as well as in many cortical and limbic areas of brain including those involved in mood and cognition. Most, but not all, of these effects were seen also upon long-term treatments of rats with sertraline or DMI. Some areas where VNS increased Delta FosB (e. g., the NTS, PBN, LC, and peripeduncular nucleus) were not affected significantly by either drug. Sertraline was similar to VNS in causing an increase in the DRN whereas DMI did not. Double-labeling of the DRN with Delta FosB and an antibody for serotonin revealed that only a small percentage of Delta FosB staining in the DRN colocalized with serotonergic neurons. The effects of VNS were somewhat more widespread than those caused by the antidepressants. The increases in Delta FosB produced by VNS were either equivalent to and/or more robust than those seen with antidepressants.