Dopamine versus Norepinephrine - Role of Dopamine beta-hydroxylase

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.

Affective Disorders

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.

• 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. Research in DBH has suggested that excess dopamine may distinguish bipolar depression from unipolar depression.
  • Bipolar disorder. Decreased DBH activity has been shown to be associated with the severity of bipolar disorder.
  • 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.

Cognition

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. 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. Sensitivity to amphetamines has shown to result from the balance of dopamine and norepinephrine.

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. 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.

Behavior

Neurological disorders. DBH activity tends to be lower in people suffering from neurological disease than in their healthy counterparts. 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.

Physical Symptoms

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.

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. 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.

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