Dopamine is a pleiotropic neurotransmitter with essential roles in motivation, reward, movement, cognition, and the modulation of prolactin. Often incorrectly referred to as 'the pleasure molecule'; dopamine is best associated with the ‘want’ to do something, rather than the ‘liking’ or pleasure associated with doing something.1,2
Dopamine disturbances
Due to its many essential functions, disturbances in dopamine activity can have profound health effects. For example, adult animals with damage to their dopamine system become akinetic (a loss in the normal ability to move muscles) and, if not artificially fed, will die of starvation.3
Dopaminergic disturbances are common, whereby researchers have described the increasing problem associated with a ‘hypodopaminergic society’.4 (See Table 1)
The physiology of dopamine
The synthesis of dopamine is complex, and there are several steps in its production, breakdown, transportation, and communication that can go askew. (See Figure 1.)
Figure 1. Dopamine synthesis and degradation
The precursors to dopamine are the amino acids phenylalanine and tyrosine. Phenylalanine is converted into tyrosine by the enzyme phenylalanine hydroxylase (PAH), and then tyrosine is converted into L-Dopa by the enzyme tyrosine hydroxylase (TH). Both PAH and TH require another enzyme known as tetrahydrobiopterin (BH4), and methylation is important to produce adequate levels of BH4.5 In the final step of its synthesis, L-dopa is converted into dopamine, whichrequiresanotherenzymecalledL-dopadecarboxylase.Otherimportantenzymesinvolvedindopaminemetabolismarecatechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). These enzymes break down dopamine into its inactive metabolites.
Dopamine transmission
From a transmission standpoint, dopamine binds to postsynaptic and/or presynaptic receptors. Dopamine also has transporters that incorporate it into synaptic vesicles and the cellular cytosol, such as vesicular monoamine transport 2 (VMAT2) and the dopamine transporter.6 Given these several crucial mechanisms, problems associated with dopamine can be due to disturbances in the concentrations of its precursors, enzymes involved in its synthesis, enzymes involved in its breakdown, receptor sensitivity, and/or transporters. (See Figure 2.)
Disorders associated with dopaminergic disturbances
Dopamine disturbances have been implicated in an extensive range of conditions. For example, dopamine seems to play a role in addictions to illicit drugs, nicotine, alcohol, certain foods, gambling, pornography, and even internet addiction.2,3
In drug addiction research, imaging studies have found that faster increases in dopamine after drug use are associated with a more reinforcing effect from the drug. Gamblers also have a higher rate of dopamine turnover than non-gamblers.7 Several mental health disorders are associated with dopamine disturbances. Anhedonia, an inability to feel pleasure, is a core feature of major depressive disorder, and dopamine plays
a pivotal role in hedonic deficits and the drive to do things. Disturbances in dopamine have also been identified in bipolar disorder, schizophrenia, attention deficit hyperactivity disorder (ADHD), Alzheimer’s disease, Parkinson’s disorder, and restless legs syndrome.8-11
Assessment and treatment of dopaminergic disturbances
The simplistic approach to alter dopaminergic activity is to prescribe pharmaceutical medications such as antipsychotics, antidepressants, anticonvulsants, and L-dopa. Unfortunately, this approach does not necessarily treat the causes of dopaminergic disturbances and is associated with many side effects. See Table 3. for a list of ways to support dopamine regulation.
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