Dopamine and Noradrenaline in the Brain; Overlapping or Dissociate Functions?

Abstract

Dopamine and noradrenaline are crucial neuromodulators controlling brain states, vigilance, action, reward, learning, and memory processes. Ventral tegmental area (VTA) and Locus Coeruleus (LC) are canonically described as the main sources of dopamine (DA) and noradrenaline (NA) with dissociate functions. A comparison of diverse studies shows that these neuromodulators largely overlap in multiple domains such as shared biosynthetic pathway and co-release from the LC terminals, convergent innervations, non-specificity of receptors and transporters, and shared intracellular signaling pathways. DA-NA interactions are mainly studied in prefrontal cortex and hippocampus, yet it can be extended to the whole brain given the diversity of catecholamine innervations. LC can simultaneously broadcast both dopamine and noradrenaline across the brain. Here, we briefly review the molecular, cellular, and physiological overlaps between DA and NA systems and point to their functional implications. We suggest that DA and NA may function in parallel to facilitate learning and maintain the states required for normal cognitive processes. Various signaling modules of NA and DA have been targeted for developing of therapeutics. Understanding overlaps of the two systems is crucial for more effective interventions in a range of neuropsychiatric conditions.

The Neuromelanin Paradox and Its Dual Role in Oxidative Stress and Neurodegeneration

“…Both DA and NA essential neurotransmitters involved in the regulation of brain states related to vigilance, action, reward, learning, and memory processes [ 105 ]. However, small amounts of these neuromodulators can be further oxidized by reactive oxygen species, yielding o-quinones that renders dihydroxyindole by cyclation and then 5,6-indolequinone or add l -cysteine that are able to polymerize and crosslink [ 80 , 106 ].…”

Noradrenergic Source of Dopamine Assessed by Microdialysis in the Medial Prefrontal Cortex

“…Different pharmacological treatments, such as psychostimulants ( Darracq et al, 1998 ), antipsychotic drugs ( Westerink et al, 1998 ; Devoto et al, 2003 ), fluoxetine ( Bymaster et al, 2002 ), stress ( Finlay et al, 1995 ; Feenstra, 2000 ), aversive and rewarding conditioned and unconditioned stimuli (see Fenstra, 2000 ) have been shown to produce concomitant and parallel changes in extracellular NE and DA in the PFC, suggesting a cross-talk between dopaminergic and noradrenergic systems to modulate the activity of target neurons in the PFC ( Guiard et al, 2008 ; Masana et al, 2011 ; Chandler et al, 2014 ; Xing et al, 2016 ; Ranjbar-Slamloo and Fazlali, 2020 ).…”

Go with the flow: A neuroscientific view on being fully engaged

“…The LC is a small nucleus in the pons of the brain and is the principle site of central norepinephrine (noradrenaline) release (Benarroch, 2009). The LC has widespread connections to other brain areas such as the amygdala and hippocampus, the cerebellum, the cerebral cortex and also the ventral tegmental area, which we identified in the previous section as the origin of dopamine cells that feed into other reward-related structures (Ranjbar-Slamloo & Fazlali, 2020).…”