Ranjbar-Slamloo Yadollah, Fazlali Zeinab
Eccles Institute of Neuroscience, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
Department of Biomedical Engineering, Columbia University, New York, NY, United States.
Front Mol Neurosci. 2020 Jan 21;12:334. doi: 10.3389/fnmol.2019.00334. eCollection 2019.
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.
多巴胺和去甲肾上腺素是控制脑状态、警觉性、行动、奖赏、学习和记忆过程的关键神经调质。腹侧被盖区（VTA）和蓝斑（LC）通常被描述为具有不同功能的多巴胺（DA）和去甲肾上腺素（NA）的主要来源。对各种研究的比较表明，这些神经调质在多个领域有很大重叠，如共享生物合成途径、从LC终末共同释放、汇聚性神经支配、受体和转运体的非特异性以及共享细胞内信号通路。DA-NA相互作用主要在前额叶皮质和海马体中进行研究，但鉴于儿茶酚胺神经支配的多样性，其研究范围可扩展至整个大脑。LC能够同时在全脑释放多巴胺和去甲肾上腺素。在此，我们简要回顾DA和NA系统之间的分子、细胞和生理重叠，并指出其功能意义。我们认为，DA和NA可能并行发挥作用，以促进学习并维持正常认知过程所需的状态。NA和DA的各种信号模块已成为治疗药物开发的靶点。了解这两个系统的重叠对于更有效地干预一系列神经精神疾病至关重要。
