Noradrenergic system

Naritoku et al. (1995) investigated regional c-Fos immunoreactivity and reported activation of the locus coeruleus (LC) by therapeutic VNS. By means of lesion studies in animal models of epilepsy, Krahl and coworkers have demonstrated that the antiseizure effect of injected norepinephrine depends on the vagus (Krahl et al., 2000) and that the seizure-attenuating effect of VNS is mediated by and totally depends on LC activity (Krahl et al., 1998). The locus coeruleus is the major origin of the noradrenergic system in the brain and has projections to brain regions which are involved in both mood regulation and epileptogenesis (e.g. thalamus, hippocampus, amygdala and isocortex). Norepinephrine has an inhibitory influence on postsynaptic neurons which may explain the antiseizure effect of activating the LC by VNS. At the same time, the noradrenergic system is involved in neuropsychiat-ric disorders like depression: one major effect of tricyclic antidepressant medication is to increment the 'noradrenergic tone' of the brain (Schatzberg and Schildkraut, 1996). Thus, roughly speaking, VNS is supposed to stimulate LC neurons, which in turn increase the delivery of norepinephrine which is supposed to be an endogenous antidepressant and anticonvulsant.

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