Current perspectives of the roles of the central norepinephrine system in anxiety and depression

Abstract

Norepinephrine (NE) is a major monoamine neurotransmitter that has widespread effects across multiple brain areas to regulate arousal and stress responses. The underlying function of the NE cortical system is to balance vigilance/scanning behavior with focused attention on novel environmental stimuli and the state of arousal. The central NE system is involved intrinsically with the stress response system, and dysregulation within the NE system has been implicated in the pathogenesis of anxiety and depressive disorders. Central NE activity paradoxically has either anxiogenic or anxiolytic effects, depending on whether the time course of the stress is acute or chronic, whether the stress is predictable or unpredictable, and which underlying brain regions are affected. Under conditions of chronic stress, NE system activity dysregulation of the hypothalamic-pituitary-adrenal system may turn a homeostatic stress response into a pathological stress response. Data suggest that the NE interplay with the serotonin system may exert neurobiological normalization of the pathophysiological state of anxious depression. Accordingly, pharmacological interventions targeting the NE system can result in anxiolytic, rather than anxiogenic, outcomes when used to treat patients with anxiety and depression. Depression and Anxiety 27:339-350, 2010. r r

Conus Venom Peptide Pharmacology

“…-Conopeptides are small hydrophobic peptides that selectively inhibit the transport of noradrenaline by NET, an important target for drugs treating a range of neurological diseases, including depression, anxiety, obsessive-compulsive disorder, and attention deficit hyperactivity disorder (Goddard et al, 2010). -MrIA and -MrIB noncompetitively inhibit NET (Sharpe et al, 2001), providing opportunities to regulate NET efficiently, irrespective of the concentration of noradrenaline present.…”

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

“…Release of NE is further modulated by the presence of presynaptic and postsynaptic α 2 (Gαi) autoreceptors that inhibit NE release upon binding NE (Arima et al, 1998;Goddard et al, 2010;Grigg et al, 1996). Conversely, α 1 (Gαq) and β 1-3 (Gαs) adrenergic receptors are expressed postsynaptically causing mobilization of intracellular Ca 2+ or cAMP, respectively.…”

Kinase-dependent Regulation of Monoamine Neurotransmitter Transporters

“…NE plays a prominent role in arousal, attention, executive function, and stress responses (Harley, 2004;Viggiano et al, 2004a;Morilak et al, 2005), with disorders such as ADHD, posttraumatic stress disorder. and depression often linked to disrupted central nervous system NE signaling (Southwick et al, 1999;Kim et al, 2008;Goddard et al, 2010). Prominent peripheral roles of 5-HT and NE are also known, as for example the role of the former in gut and platelet function (Mercado and Kilic, 2010;Mawe and Hoffman, 2013), and of the latter in broad control of autonomic function including heart rate, vasoconstriction, and lipolysis (Goldstein et al, 1983).…”