Dopamine versus Norepinephrine - Role of Dopamine beta-hydroxylase

From brainmatrix

Delineating the effects of changes in dopamine and changes in norepinephrine is complicated by the fact that dopamine is a precursor to norepinephrine. Thus, information on the role of dopamine β-hydroxylase (DBH), which is the enzyme that converts dopamine to norepinephrine, is important for distinguishing the specific implications of alterations in dopamine versus norepinephrine signaling.[1]

Affective Disorders[edit]

Psychiatric disease. DBH levels have been observed to be altered in patients with psychiatric diseases, suggesting that norepinephrine or epinephrine may play a critical role in these diseases.[2]

  • Depression. People with bipolar depression have been shown to have low levels of DBH specifically during mania, suggesting that acute changes in norepinephrine or epinephrine could contribute to or result from specific psychiatric symptoms. Those with depression have been observed to have higher levels of DBH.[2] Research in DBH has suggested that excess dopamine may distinguish bipolar depression from unipolar depression.[3]
    • Bipolar disorder. Decreased DBH activity has been shown to be associated with the severity of bipolar disorder.[3][4]
    • Psychotic depression. Those with psychotic depression are more likely to have lower serum DBH activity than those with nonpsychotic depression, suggesting that norepinephrine levels may play a role in psychosis.
  • Schizophrenia. Consistent with a potential role of norepinephrine levels in psychosis, people with schizophrenia have been observed to have lower levels of DBH.[2]


Both dopamine and norepinephrine are important for attention and learning. They interact functionally in the prefrontal cortex, which is important for cognition and executive functioning.[5] Both are implicated in ADHD, based on the pharmacological treatments, many of which increase the availability of these neurotransmitters in the synaptic cleft and raise their levels in the prefrontal cortex.[6][7] Sensitivity to amphetamines has shown to result from the balance of dopamine and norepinephrine.[8]

Evidence suggests that dopamine and norepinephrine may contribute differently to attention and learning depending on the context and may contribute in distinct ways within specific contexts.[9][10] For instance, norepinephrine appears to be involved in odor preference learning and defensive conditioning, whereas dopamine appears to be more important for auditory cortex remodeling.[9]


Neurological disorders. DBH activity tends to be lower in people suffering from neurological disease than in their healthy counterparts.[11][2] The specific causes and implications of this abnormality are not clearly understood. For instance, whether neurological disease causes a reduction in DBH activity or vice versa is not known.

Locomotor activity. Knockout studies that enable mice to show increased norepinephrine and decreased dopamine levels or vice versa have demonstrated that locomotor activity tends to depend specifically on dopamine rather than norepinephrine.[8]

Physical Symptoms[edit]

Immunity. Dopamine and norepinephrine appear to have distinct roles in immune functioning. For instance, mice that lack DBH and can therefore produce dopamine but not norepinephrine or epinephrine are more susceptible to infection and have impaired T-cell function, which includes impaired production of the protective Th1 cell cytokines.[12]

Orthostatic hypotension. People who are deficient in DBH are deficient in the autonomic regulation of cardiovascular functioning, suggesting that norepinephrine or epinephrine may play a role in this type of regulation.[13][14] This abnormality puts people at heightened risk for orthostatic hypotension.

Ptosis of eyelids. Norepinephrine or epinephrine may contribute to eyelid function, as infants, children, and adults who are deficient in DBH often have ptosis of the eyelids in combination with hypotension.[13]

Reduced exercise capacity. DBH deficiency leads to reduced exercise capacity, pointing to a potential role of norepinephrine or epinephrine in physiological functioning during exercise.[13]


  1. Rossi, John; Zolovick, A.J.; Davies, R.F.; Panksepp, J. (1982). "The role of norepinephrine in feeding behavior". Neuroscience & Biobehavioral Reviews. 6 (2): 195–204. doi:10.1016/0149-7634(82)90055-0.
  2. 2.0 2.1 2.2 2.3 Rush, R. A.; Geffen, L. B. (1980). "Dopamine β-Hydroxylase in Health and Disease". CRC Critical Reviews in Clinical Laboratory Sciences. 12 (3): 241–277. doi:10.3109/10408368009108731. ISSN 0590-8191.
  3. 3.0 3.1 Brown, A. S.; Gershon, S. (1993). "Dopamine and depression". Journal of Neural Transmission. 91 (2–3): 75–109. doi:10.1007/BF01245227. ISSN 0300-9564.
  4. Sun, Zuoli; Bo, Qijing; Mao, Zhen; Li, Feng; He, Fan; Pao, Christine; Li, Wenbiao; He, Yi; Ma, Xin; Wang, Chuanyue (2021). "Reduced Plasma Dopamine-β-Hydroxylase Activity Is Associated With the Severity of Bipolar Disorder: A Pilot Study". Frontiers in Psychiatry. 12: 566091. doi:10.3389/fpsyt.2021.566091. ISSN 1664-0640. PMC PMC8115127 Check |pmc= value (help). PMID 33995135 Check |pmid= value (help).CS1 maint: PMC format (link)
  5. Xing, Bo; Li, Yan-Chun; Gao, Wen-Jun (2016). "Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex". Brain Research. 1641: 217–233. doi:10.1016/j.brainres.2016.01.005. PMC 4879059. PMID 26790349.CS1 maint: PMC format (link)
  6. Shier, Anna C.; Reichenbacher, Thomas; Ghuman, Harinder S.; Ghuman, Jaswinder K. (2013). "Pharmacological Treatment of Attention Deficit Hyperactivity Disorder in Children and Adolescents: Clinical Strategies". Journal of Central Nervous System Disease. 5: JCNSD.S6691. doi:10.4137/JCNSD.S6691. ISSN 1179-5735. PMC 3616598. PMID 23650474.CS1 maint: PMC format (link)
  7. Wilens, Timothy E.; Spencer, Thomas J. (2010). "Understanding Attention-Deficit/Hyperactivity Disorder from Childhood to Adulthood". Postgraduate Medicine. 122 (5): 97–109. doi:10.3810/pgm.2010.09.2206. ISSN 0032-5481. PMC 3724232. PMID 20861593.CS1 maint: PMC format (link)
  8. 8.0 8.1 Viggiano, D.; Ruocco, L. A.; Arcieri, S.; Sadile, A. G. (2004). "Involvement of Norepinephrine in the Control of Activity and Attentive Processes in Animal Models of Attention Deficit Hyperactivity Disorder". Neural Plasticity. 11 (1–2): 133–149. doi:10.1155/NP.2004.133. ISSN 2090-5904. PMC 2565437. PMID 15303310.CS1 maint: PMC format (link)
  9. 9.0 9.1 Harley, Carolyn W. (2004). "Norepinephrine and Dopamine as Learning Signals". Neural Plasticity. 11 (3–4): 191–204. doi:10.1155/NP.2004.191. ISSN 2090-5904. PMC 2567044. PMID 15656268.CS1 maint: PMC format (link)
  10. Levy, Florence (2009). "Dopamine vs Noradrenaline: Inverted-U Effects and ADHD Theories". Australian & New Zealand Journal of Psychiatry. 43 (2): 101–108. doi:10.1080/00048670802607238. ISSN 0004-8674.
  11. Rahman, Khalilur (2009). "Dopamine-ß-hydroxylase (DBH), its cofactors and other biochemical parameters in the serum of neurological patients in Bangladesh". International Journal of Cardiology. 137: S28. doi:10.1016/j.ijcard.2009.09.092.
  12. Alaniz, Robert C.; Thomas, Steven A.; Perez-Melgosa, Mercedes; Mueller, Kai; Farr, Andrew G.; Palmiter, Richard D.; Wilson, Christopher B. (1999). "Dopamine β-hydroxylase deficiency impairs cellular immunity". Proceedings of the National Academy of Sciences. 96 (5): 2274–2278. doi:10.1073/pnas.96.5.2274. ISSN 0027-8424. PMC 26773. PMID 10051631.CS1 maint: PMC format (link)
  13. 13.0 13.1 13.2 Garland EM, Biaggioni I. Dopamine Beta-Hydroxylase Deficiency. GeneReviews®. Published online April 25, 2019. Accessed July 24, 2022.
  14. Kollins, Scott H.; Adcock, R. Alison (2014). "ADHD, altered dopamine neurotransmission, and disrupted reinforcement processes: Implications for smoking and nicotine dependence". Progress in Neuro-Psychopharmacology and Biological Psychiatry. 52: 70–78. doi:10.1016/j.pnpbp.2014.02.002. PMC 4004668. PMID 24560930.CS1 maint: PMC format (link)