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.
Highlights
Central nervous system produces diverse neurochemicals which bind to specific receptors coupled to the intricate intracellular signaling pathways
As knowledge of neurotransmission rapidly grew in the past few decades, it became soon clear that the actions of neurotransmitters are complex and some neurons produce and release two or more chemicals as fast neurotransmitters, neuromodulators, or neuropeptides (Vaaga et al, 2014)
Functional Overlaps of Dopamine and Noradrenaline in the Brain which are known for their binding to the fast-acting ionotropic receptors, others predominantly activate metabotropic receptors, they are commonly called neuromodulators
Summary
Central nervous system produces diverse neurochemicals which bind to specific receptors coupled to the intricate intracellular signaling pathways. Functional Overlaps of Dopamine and Noradrenaline in the Brain which are known for their binding to the fast-acting ionotropic receptors, others predominantly activate metabotropic receptors, they are commonly called neuromodulators. Noradrenaline acts on three main G-protein coupled receptors, known as β-, α-1, and α-2 adrenoceptors (Figure 1C) These receptors have complex effects on neuronal excitability and synaptic transmission, depending on their site of action and concentration of NA (Berridge and Waterhouse, 2003; Arnsten et al, 2012; Waterhouse and Navarra, 2019). Α1-adrenoceptors activate phospholipase C signaling pathway through Gq. Dopamine acts on five types of G-protein coupled receptors, D1–D5, which are categorized in two main functional classes of D1 and D2 (Beaulieu and Gainetdinov, 2011). This can be clarified by comparing the synaptic effects of DA and NA in cortex or hippocampus and identifying transporters involved in these regions
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