The role of the central noradrenergic system in behavioral inhibition

Abstract

Although the central noradrenergic system has been shown to be involved in a number of behavioral and neurophysiological processes, the relation of these to its role in depressive illness has been difficult to define. The present review discusses the hypothesis that one of its chief functions that may be related to affective illness is the inhibition of behavioral activation, a prominent symptom of the disorder. This hypothesis is found to be consistent with most previous neuropsychopharmacological and immunohistochemical experiments on active behavior in rodents in a variety of experimental conditions using manipulation of neurotransmission at both locus coeruleus and forebrain adrenergic receptors. The findings support a mechanism in which high rates of noradrenergic neural activity suppress the neural activity of principal neurons in forebrain regions mediating active behavior. The suppression may be mediated through postsynaptic galaninergic and adrenergic receptors, and via the release of corticotrophin-releasing hormone. The hypothesis is consistent with clinical evidence for central noradrenergic system hyperactivity in depressives and with the view that this hyperactivity is a contributing etiological factor in the disorder. A similar mechanism may underlie the ability of the noradrenergic system to suppress seizure activity suggesting that inhibition of the spread of neural activation may be a unifying function.

Evening types are prone to depression

“…This indicates that depression might increase the risk of morbidity among evening types. Noradrenergic transmission has been implicated as dysfunctional in depressed individuals (Checkley, 1980;Stone et al, 2011) and may underlie some of the associations we found herein such as a faster resting heart rate. However, because we did not assess any direct indicators of this transmission pathway, it remains speculative.…”

Assessment of Wakefulness and Brain Arousal Regulation in Psychiatric Research

“…Most intriguingly, symptoms of anhedonia and inhibition have also been suggested to be a consequence of noradrenergic hyperactivity [78,79] . Furthermore, the tonic hyperarousal explains the pronounced insomnia in depression, including the increased sleep onset latency [80,81] .…”

Disruption of glucocorticoid receptors in the noradrenergic system leads to BDNF up-regulation and altered serotonergic transmission associated with a depressive-like phenotype in female GRDBHCre mice

“…However, the functional meaning of this phenomenon remains unclear. Some researchers suggest overinhibition of LC neuron activity mediated by  2 -AR, which is attenuated by antidepressant treatment that targets this receptor (Cottingham and Wang, 2012); other researchers claim the contrary that the increased activity of the LC neurons may contribute to a depressive state (Stone et al, 2011). The latter hypothesis is supported by previous experiments that demonstrated the administration of  2 -AR agonists or antagonists into the LC region induces an antidepressant effect or depressive-like behavior, respectively, in the forced swimming test (FST) (Weiss et al, 1986).…”