Dopamine Imbalance Hypothesis

From: 'Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome' <a href="http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2265.2000.01049.x/full">http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2265.2000.01049.x/full</a>

From: <a href="https://me-pedia.org/wiki/Dopamine">Dopamine - MEpedia</a>

Studies have found lower levels of the dopamine precursor <a title="Tyrosine" href="https://me-pedia.org/wiki/Tyrosine">tyrosine</a><a href="https://me-pedia.org/wiki/Dopamine#cite_note-7">[7]</a> and reduced activation in the <a title="Basal ganglia" href="https://me-pedia.org/wiki/Basal_ganglia">basal ganglia</a><a href="https://me-pedia.org/wiki/Dopamine#cite_note-8">[8]</a><a href="https://me-pedia.org/wiki/Dopamine#cite_note-9">[9]</a> , the region of the brain with the highest concentration of dopaminergic neurons.

<h2>Nervous system[<a class="mw-editsection-visualeditor" title="Edit section: Nervous system" href="https://me-pedia.org/index.php?title=Dopamine&veaction=edit&section=2">edit</a> | <a title="Edit section: Nervous system" href="https://me-pedia.org/index.php?title=Dopamine&action=edit&section=2">edit source</a>]</h2>

Dopamine plays a role in executive function, motor control, motivation, arousal. The largest source of dopamine in the brain is in the <a class="new" title="Substantia nigra (page does not exist)" href="https://me-pedia.org/index.php?title=Substantia_nigra&action=edit&redlink=1">substantia nigra</a> and <a class="new" title="Ventral segmental area (page does not exist)" href="https://me-pedia.org/index.php?title=Ventral_segmental_area&action=edit&redlink=1">ventral segmental area</a>, both components of the <a title="Basal ganglia" href="https://me-pedia.org/wiki/Basal_ganglia">basal ganglia</a>.

<h2>Immune system[<a class="mw-editsection-visualeditor" title="Edit section: Immune system" href="https://me-pedia.org/index.php?title=Dopamine&veaction=edit&section=3">edit</a> | <a title="Edit section: Immune system" href="https://me-pedia.org/index.php?title=Dopamine&action=edit&section=3">edit source</a>]</h2>

Dopamine reduces systemic inflammation by blocking <a title="Inflammasome" href="https://me-pedia.org/wiki/Inflammasome">inflammasome</a> activation.<a href="https://me-pedia.org/wiki/Dopamine#cite_note-2">[2]</a><a href="https://me-pedia.org/wiki/Dopamine#cite_note-3">[3]</a>

Dopamine has a role in the activity of <a class="mw-redirect" title="Lymphocytes" href="https://me-pedia.org/wiki/Lymphocytes">lymphocytes</a>. It activates native <a class="new" title="T cells (page does not exist)" href="https://me-pedia.org/index.php?title=T_cells&action=edit&redlink=1">t cells</a> but inhibits the activity of activated t cells.<a href="https://me-pedia.org/wiki/Dopamine#cite_note-4">[4]</a> However, dopamine may also induce the release of <a class="new" title="Interleukin-17 (page does not exist)" href="https://me-pedia.org/index.php?title=Interleukin-17&action=edit&redlink=1">interleukin-17</a> in <a title="Rheumatoid arthritis" href="https://me-pedia.org/wiki/Rheumatoid_arthritis">rheumatoid arthritis</a>.<a href="https://me-pedia.org/wiki/Dopamine#cite_note-5">[5]</a>

Inflammation may also have a role in dopamine production. A study of <a title="Hepatitis C" href="https://me-pedia.org/wiki/Hepatitis_C">Hepatitis C</a> patients found that <a class="new" title="Interferon alpha (page does not exist)" href="https://me-pedia.org/index.php?title=Interferon_alpha&action=edit&redlink=1">interferon alpha</a> treatment resulted in significantly increased levels of <a class="new" title="Dihydrobiopterin (page does not exist)" href="https://me-pedia.org/index.php?title=Dihydrobiopterin&action=edit&redlink=1">dihydrobiopterin</a>(BH2) and decreased <a title="Tetrahydrobiopterin" href="https://me-pedia.org/wiki/Tetrahydrobiopterin">tetrahydrobiopterin</a> (BH4) as well as reduced conversion of <a title="Phenylalanine" href="https://me-pedia.org/wiki/Phenylalanine">phenylalanine</a> to <a title="Tyrosine" href="https://me-pedia.org/wiki/Tyrosine">tyrosine</a> in the cerebrospinal fluid, which are associated with decreased dopamine in the brain.<a href="https://me-pedia.org/wiki/Dopamine#cite_note-6">[6]</a>

Mice fed a ketogenic diet had increased activity of dopaminergic neurons.[17]

<h2>Dopamine synthesis[<a class="mw-editsection-visualeditor" title="Edit section: Dopamine synthesis" href="https://me-pedia.org/index.php?title=Dopamine&veaction=edit&section=1">edit</a> | <a title="Edit section: Dopamine synthesis" href="https://me-pedia.org/index.php?title=Dopamine&action=edit&section=1">edit source</a>]</h2>

Dopamine is synthesized in neurons and the adrenal glands.

L-<a title="Phenylalanine" href="https://me-pedia.org/wiki/Phenylalanine">Phenylalanine</a> → L-<a title="Tyrosine" href="https://me-pedia.org/wiki/Tyrosine">Tyrosine</a> → <a class="new" title="L-DOPA (page does not exist)" href="https://me-pedia.org/index.php?title=L-DOPA&action=edit&redlink=1">L-DOPA</a> → Dopamine

Dopamine is incapable of cross the blood-brain barrier so must be produced in the brain for neuronal activity or peripherally for peripheral activity.

Peripheral dopamine is produced by the <a title="Adrenal glands" href="https://me-pedia.org/wiki/Adrenal_glands">adrenal glands</a> and the <a class="mw-redirect" title="Gut" href="https://me-pedia.org/wiki/Gut">gut</a>.

<a class="new" title="BH4 (page does not exist)" href="https://me-pedia.org/index.php?title=BH4&action=edit&redlink=1">BH4</a> is a cofactor in the conversion of L-Phenylalanine to L-Tyrosine and L-Tyrosine to L-DOPA. The availability of BH4 is dependent on the <a title="Methylation cycle" href="https://me-pedia.org/wiki/Methylation_cycle">methylation cycle</a>.

Dopamine is a precursor to <a title="Norepinephrine" href="https://me-pedia.org/wiki/Norepinephrine">norepinephrine</a> and <a title="Epinephrine" href="https://me-pedia.org/wiki/Epinephrine">epinephrine</a>.

<a title="Iron" href="https://me-pedia.org/wiki/Iron">Iron</a> is important in the expression of dopamine receptors in the brain<a href="https://me-pedia.org/wiki/Dopamine#cite_note-1">[1]</a> and is also a cofactor in for <a class="new" title="Tyrosine hydroxylase (page does not exist)" href="https://me-pedia.org/index.php?title=Tyrosine_hydroxylase&action=edit&redlink=1">tyrosine hydroxylase</a>, the enzyme that catalyzes the conversion of tyrosine to L-DOPA.