Department of Pharmacology, the University of Texas Health Science Center, San Antonio, Texas, USA.
J Pharmacol Exp Ther. 2012 May;341(2):317-25. doi: 10.1124/jpet.111.188953. Epub 2012 Jan 27.
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, ΔFosB 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 ΔFosB and serotonin was used to determine whether serotonergic neurons in the dorsal raphe nucleus (DRN) were activated by long-term VNS. VNS significantly increased ΔFosB 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 ΔFosB (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 ΔFosB and an antibody for serotonin revealed that only a small percentage of ΔFosB 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 ΔFosB produced by VNS were either equivalent to and/or more robust than those seen with antidepressants.
迷走神经刺激（VNS）已被批准用于治疗难治性抑郁症。然而，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很少，如果有的话。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，使用 ΔFosB 免疫组织化学来评估长期给予 VNS 激活的不同脑区。将 VNS 的作用与舍曲林或去甲丙咪嗪（DMI）引起的作用进行了比较。使用 ΔFosB 和 5-羟色胺的双重标记来确定长期 VNS 是否激活中缝背核（DRN）中的 5-羟色胺能神经元。VNS 显著增加了孤束核（NTS）、臂旁核（PBN）、蓝斑核（LC）和 DRN 以及大脑的许多皮质和边缘区域中的 ΔFosB 染色，这些区域与情绪和认知有关。大多数（但不是全部）这些作用也见于长期用舍曲林或 DMI 治疗的大鼠。VNS 增加 ΔFosB 的一些区域（例如 NTS、PBN、LC 和 Peripeduncular 核）不受任何一种药物的显著影响。舍曲林在引起 DRN 中 ΔFosB 增加方面与 VNS 相似，而 DMI 则没有。用 ΔFosB 和 5-羟色胺抗体对 DRN 进行双重标记显示，DRN 中只有一小部分 ΔFosB 染色与 5-羟色胺能神经元共定位。VNS 的作用比抗抑郁药更为广泛。VNS 产生的 ΔFosB 增加与抗抑郁药引起的增加相当或更强。
