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, ⌬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 ⌬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 ⌬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 ⌬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. Doublelabeling of the DRN with ⌬FosB and an antibody for serotonin revealed that only a small percentage of ⌬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 ⌬FosB produced by VNS were either equivalent to and/or more robust than those seen with antidepressants.

Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part III

“…Cunningham et al reported short‐term VNS (2 hours) in rats activated the nucleus of the solitary tract (NST), paraventricular nucleus of the hypothalamus, parabrachial nucleus (PBN), ventral bed nucleus of the stria terminalis, and locus coeruleus (LC) . Long‐term VNS (2‐3 weeks) activated all of the above regions as well as the cingulate cortex, ventrolateral periaqueductal gray (PAG), and dorsal raphe nucleus (DRN), reflecting the potential VNS action sites and a differential temporal response between noradrenergic and serotonergic neurons. Also, six‐day preemptive NST stimulation delayed epileptogenesis in cats .…”

Vagus nerve stimulation to augment recovery from severe traumatic brain injury impeding consciousness: a prospective pilot clinical trial

“…51 In addition, acute VNS induced specific expression of nuclear fos gene that is an immediate early gene and a marker for neuronal activation in several forebrain structures, including the amygdala, cingulate cortex, hypothalamus, the brainstem, locus ceruleus, noradrenergic nuclei, and thalamus. 52 Chronic VNS significantly increased staining of ΔFosB (a marker of chronic neuronal activation) bilaterally in tractus solitarius, locus ceruleus, parabrachial nucleus, dorsal raphe nuclei, and in many cortical and limbic areas of brain including those involved in mood and cognition 53,54 . The VNS effects were more widespread than those caused by the antidepressants.…”

“…The VNS effects were more widespread than those caused by the antidepressants. 54 Locus ceruleus neurons impact Fos protein expression, suggesting a plastic mechanism for diminishing epileptogenesis. 55 These structures activated by the vagus may play an important role in the control of epilepsy, recognition memory, and control of arousal 47,56,57 .…”

Vagus Nerve Stimulation Exerts the Neuroprotective Effects in Obese-Insulin Resistant Rats, Leading to the Improvement of Cognitive Function

“…Furthermore, VNS in model of depression increased neurogenesis and enhanced neural activity in many brain areas involving cognition2223. Moreover, VNS in normal rats has been shown to modulate neuronal plasticity and increased dendritic complexity24.…”