Comparison of ΔFosB Immunoreactivity Induced by Vagal Nerve Stimulation with That Caused by Pharmacologically Diverse Antidepressants

Abstract

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.