Cellular and Molecular Neurobiology

, Volume 39, Issue 1, pp 31–59 | Cite as

Dopamine: Functions, Signaling, and Association with Neurological Diseases

  • Marianne O. Klein
  • Daniella S. Battagello
  • Ariel R. Cardoso
  • David N. Hauser
  • Jackson C. BittencourtEmail author
  • Ricardo G. CorreaEmail author
Review Paper


The dopaminergic system plays important roles in neuromodulation, such as motor control, motivation, reward, cognitive function, maternal, and reproductive behaviors. Dopamine is a neurotransmitter, synthesized in both central nervous system and the periphery, that exerts its actions upon binding to G protein-coupled receptors. Dopamine receptors are widely expressed in the body and function in both the peripheral and the central nervous systems. Dopaminergic signaling pathways are crucial to the maintenance of physiological processes and an unbalanced activity may lead to dysfunctions that are related to neurodegenerative diseases. Unveiling the neurobiology and the molecular mechanisms that underlie these illnesses may contribute to the development of new therapies that could promote a better quality of life for patients worldwide. In this review, we summarize the aspects of dopamine as a catecholaminergic neurotransmitter and discuss dopamine signaling pathways elicited through dopamine receptor activation in normal brain function. Furthermore, we describe the potential involvement of these signaling pathways in evoking the onset and progression of some diseases in the nervous system, such as Parkinson’s, Schizophrenia, Huntington’s, Attention Deficit and Hyperactivity Disorder, and Addiction. A brief description of new dopaminergic drugs recently approved and under development treatments for these ailments is also provided.


Dopamine pathway Neurotransmitter Central nervous system Neurodegenerative diseases 



Alzheimer’s disease


Attention deficit/hyperactivity disorder


Aldehyde dehydrogenase


Brain-derived neurotropic factor


Calcium/calmodulin-dependent kinase II


Cyclic 3,5 adenine-monophosphate


Cyclin-dependent kinase 5


Casein kinase 1


Casein kinase 2


Catechol-O-methyl transferase


cAMP Response element-binding protein


Cerebral spinal fluid




cAMP-Regulated phosphoprotein 32-kDa


Dopamine transporter


PARK7 (Parkinson disease protein 7)


3,4-Dihydroxyphenylacetic acid




Glutamine, leucine, lysine, and serine-rich protein


Extracellular-signal regulated kinases


US Food and Drug Administration


γ-Amino butyric acid


G protein inwardly rectifying potassium channel


G protein-coupled receptor


G protein-coupled receptor kinase


Glycogen synthase kinase 3


Glutathione transferase


Guanosine triphosphate


Homovanillic acid


Huntington’s disease


Huntingtin gene


Insulin growth factor


Inositol trisphosphate


c-Jun kinase




Lewy bodies


Leucine-rich repeat kinase 2


Mitogen-activated protein kinase


Microtubule-associated protein


Monoamine transporter


Monoamine oxidase


mTOR complex 2


Nucleus accumbens


Norepinephrine transporter


Glutamate N-methyl-d-aspartate




Parkinson’s disease


Phosphatidylinositol-dependent kinase 1






Protein kinase A


Protein kinase C


Phospholipase C


Protein phosphatase 1


Protein phosphatase 2A


Protein phosphatase 2B


Regulators of G protein signaling


Rab3a-interacting molecule


Reactive oxygen species


Receptor tyrosine kinase




Striatal-enriched tyrosine phosphatase




Trace amine-associated receptors


Vesicular monoamine transporter


Ventral tegmental area



This review was supported by São Paulo State Foundation for the Support of Research (FAPESP, Brazil; Grant #2016/02224-1 to JCB, Grant #2017/17998-5 to MOK, and Grant #2017/18019-0 to ARC). DSB is a fellowship recipient of the Agency for the Advancement of Higher Education (CAPES, Brazil). JCB is a recipient of grants from the National Council for Scientific and Technological Development (CNPq, Brazil; Grant #426378/2016-4), CAPES, and the Comité Français d’Evaluation de la Coopération Universitaire avec le Brésil (French Committee for the Evaluation of Academic and Scientific Cooperation with Brazil; CAPES-COFECUB Grant #848/15). RGC was partially supported by a Special Visiting Researcher (PVE) grant from the “Science without Borders” Program (CAPES).

Author Contributions

In this review, all authors had full access to the data and take all responsibility for its integrity and accuracy. MOK, DSB, and ARC drafted the manuscript, under supervision of JCB and RGC. MOK and DSB conceptualized and designed the figures. DNH, JCB, and RGC made critical revisions of the manuscript for their relevant intellectual content. JCB and RGC obtained the funding. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical SciencesUniversity of São Paulo (USP)São PauloBrazil
  2. 2.Center for Translational NeuroscienceSanford Burnham Prebys (SBP) Medical Discovery InstituteLa JollaUSA
  3. 3.Center for Neuroscience and Behavior, Institute of PsychologyUSPSão PauloBrazil

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