Dopamine

Dopamine is a catecholamine neurotransmitter, classified with other neurotransmitters like norepinephrine and epinephrine. A series of hydroxylases synthesize dopamine from the amino acid tyrosine to L-DOPA, dopamine’s precursor. Dopamine production takes place across the body by dopaminergic cells in your nervous system, your kidneys,¹ and gastrointestinal tract². Dopamine acts by binding to one of five types of dopamine receptors to mediate dopamine activity³. Dopamine activity also occurs when dopamine binds to adrenergic receptors in the heart and other organs⁴.

Dopamine plays various functions across the human brain. Dopamine contributes to cognitive control in the prefrontal cortex by binding to D1R and D2R, two kinds of dopamine receptors⁵. Dopamine also acts as a chemical messenger. Dopamine travels through the bloodstream to activate prolactin inhibiting hormone and prolactin inhibiting factor production⁶. Both prevent prolactin secretion at the anterior pituitary gland.

Dopamine and drug addiction

In the central nervous system, extracellular vesicles release dopamine from the presynaptic neuron. Upon dopamine release, the neurotransmitter binds to dopamine at the postsynaptic neuron. Each of these components are essential for the brain’s reward system—the process by which neurons in the ventral tegmental area of the brain communicate with neurons in the nucleus accumbens⁷. An aberrant reward system that causes low dopamine levels can drives drug abuse from poor impulse control⁸. Addictive drugs raise dopamine levels when a person struggles to feel reward from a given activity.

Dopamine and mental disorders

High and low dopamine levels are associated with multiple mental disorders⁹. Individuals with attention deficit hyperactivity disorder have polymorphisms that alter dopamine receptors, reducing dopamine system activity in dopamine pathways¹⁰. Individuals with major depressive disorder also do not produce enough dopamine, reporting lowered feelings of satisfaction and pleasure¹¹.

On the other hand, too much dopamine increases the likelihood of experiencing delusions and hallucinations in schizophrenia¹². Furthermore, mouse models have demonstrated that increased dopamine levels are associated with worsened symptoms in anxiety disorders¹³. For these reasons, researchers have developed dopamine antagonists to treat schizophrenia and bipolar disorder. Dopamine antagonists block dopamine receptors, reducing dopamine activity.

Dopamine and neurodegenerative diseases

Dopamine plays an important role in neurodegenerative diseases. Increased dopamine catabolism into DOPAL can worsen alpha-synuclein aggregation and reduce brain dopamine levels in Parkinson’s Disease patients¹⁴. As Parkinson’s Disease progresses, dopaminergic neurons also degenerate, lowering dopamine levels¹⁵. One therapeutic approach to counter the dopamine imbalance employs L-Dopa, the precursor to dopamine molecules. The drug enters the substantia nigra pars compacta through the blood brain barrier where the central nervous system converts Levodopa to dopamine¹⁶. As a result, more dopamine is present in the brain to boost dopamine levels even as the brain degenerates.

References

1. Harris RC and Zhang MZ. Dopamine, the Kidney, and Hypertension. Curr Hypertens Rep 2012;14(2):138-143. doi:10.1007/s11906-012-0253-z
2. Eisenhofer G, Åneman A, Friberg P, et al. Substantial Production of Dopamine in the Human Gastrointestinal Tract. J Clin Endocrinol Metab 1997;82(11):3864-3871. doi:10.1210/jcem.82.11.4339
3. Bhatia A, Lenchner JR, Saadabadi A. Biochemistry, Dopamine Receptors. In: StatPearls. StatPearls Publishing; 2023. Accessed July 17, 2023. http://www.ncbi.nlm.nih.gov/books/NBK538242/
4. Cornil CA, Ball GF. Interplay among catecholamine systems: Dopamine binds to α2-adrenergic receptors in birds and mammals. J Comp Neurol 2008;511(5):610-627. doi:10.1002/cne.21861
5. Ott T, Nieder A. Dopamine and Cognitive Control in Prefrontal Cortex. Trends Cogn Sci 2019;23(3):213-234. doi:10.1016/j.tics.2018.12.006
6. Ben-Jonathan N, Hnasko R. Dopamine as a Prolactin (PRL) Inhibitor. Endocr Rev 2001;22(6):724-763. doi:10.1210/edrv.22.6.0451
7. Lewis RG, Florio E, Punzo D, Borrelli E. The Brain’s Reward System in Health and Disease. Adv Exp Med Biol 2021;1344:57-69. doi:10.1007/978-3-030-81147-1_4
8. Wise RA and Robble MA. Dopamine and Addiction. Annu Rev Psychol 2020;71:79-106. doi:10.1146/annurev-psych-010418-103337
9. Worley J. The Role of Pleasure Neurobiology and Dopamine in Mental Health Disorders. J Psychosoc Nurs Ment Health Serv 2017;55(9):17-21. doi:10.3928/02793695-20170818-09
10. Wu J, Xiao H, Sun H et al. Role of Dopamine Receptors in ADHD: A Systematic Meta-analysis. Mol Neurobiol 2012;45(3):605-620. doi:10.1007/s12035-012-8278-5
11. Belujon P and Grace AA. Dopamine System Dysregulation in Major Depressive Disorders. Int J Neuropsychopharmacol 2017;20(12):1036-1046. doi:10.1093/ijnp/pyx056
12. Brisch R, Saniotis A, Wolf R et al. The Role of Dopamine in Schizophrenia from a Neurobiological and Evolutionary Perspective: Old Fashioned, but Still in Vogue. Front Psychiatry 2014;5:47. doi:10.3389/fpsyt.2014.00047
13. Yorgason JT, España RA, Konstantopoulos JK et al. Enduring increases in anxiety-like behavior and rapid nucleus accumbens dopamine signaling in socially isolated rats. Eur J Neurosci 2013;37(6):1022-1031. doi:10.1111/ejn.12113
14. Masato A, Plotegher N, Boassa D et al. Impaired dopamine metabolism in Parkinson’s disease pathogenesis. Mol Neurodegener 2019;14(1):35. doi:10.1186/s13024-019-0332-6
15. Mamelak M. Parkinson’s Disease, the Dopaminergic Neuron and Gammahydroxybutyrate. Neurol Ther 2018;7(1):5-11. doi:10.1007/s40120-018-0091-2
16. Fahn S. The history of dopamine and levodopa in the treatment of Parkinson’s disease. Mov Disord 2008;23(S3):S497-S508. doi:10.1002/mds.22028