yana-notes

Dopamine

links: Neurotransmitter Catecholamine reference:

Dopamine 120 #

  • Has 5 receptors (all metabotropic): D1 to D5; D2 being the Autoreceptor. D1 consists of 2 subtypes: D1 & D5; D2 consisting of D2, D3, & D4.

600

Metabolism #

Iron #

  • The role of metal ions in dopaminergic neuron degeneration in Parkinsonism and Parkinson’s disease this topic is epic. Dopamine neurotoxicity relies on fenton reactions.
    • Manganese 3+ is a strong oxidizing agent, which oxidizes Dopamine to aminochrome (dopaminochrome), the precursor of Neuromelanin, a polymer of 5,6-dihydroxyindole. R
      • Neuromelanin blocks the hydroxyl production via Fenton Reaction, and inhibits iron-mediated oxidation of Ascorbic acid, and the complexing prevents dopamine oxidation itself.
    • Copper is able to complex with dopamine inducing caspase-independent cell death with formation of autophagic vacuoles.
      • Copper inhibits the vesicular H(+)-ATPase required for dopamine transport via VMAT2, resulting in an increase of free cytosolic dopamine and its subsequent oxidation
      • Binds with high affinity to Amyloid β, promoting its oligomerization and neurotoxicity.
    • Iron is able to complex with dopamine as well in the extracellular space.
      • 500 copper has the same cascade, besides the Fenton reaction: formation of the hydroxyl radical via ferrous iron and Hydrogen Peroxide: $\ce{Fe^{2+} + H2O2 -> Fe^{3+} + ^{.}OH + OH^-}$ (and similar things), and like using $\ce{Cu^{+}}$.
      • There is also $\ce{Fe^{3+} + H2O2 -> Fe^{2+} + HOO^{.} + H^+}$, forming the hydroperoxyl radical.
      • Not shown here is oxidopamine/6-OHDA, which converts to and from dopamine–quinone and into aminochrome: 150
        • Its rate increases with more acidic pH. Which is counterintuitive if pH and redox potential are to have an inverse relationship.
      • Ferritin Heavy Chain overexpression in dopamine neurons is neuroprotective.
      • Lisuride protects against iron-induced lesions.
      • Noradrenaline competes with dopamine for(/with?) Fe3+, forming a complex that is not neurotoxic.
    • VMAT2 sequesters iron in an acidic environment, where oxidation is not possible:
  • 500
  • Iron and dopamine: a toxic couple (lol)
    • Neurodegeneration in the affected regions may result from the potent redox couple formed by iron and dopamine itself
  • Dopamine and DOPA cause release of iron from ferritin and lipid peroxidation of liposomes
    • Funny: high DA/DOPA concentrations inibited the iron-lipid peroxidation. There must be a curve

Behavior #

  • DA does not signal reward per se but rather mediates a learning signal that allows the system to predict better when rewards are likely to occur and thereby contribute to the optimization of reward-seeking behaviors R
  • See Histamine and its behavioral effects. Has some important interactions with Histamine. High histamine usually means low dopamine, but high dopamine doesn’t necessarily mean low histamine. Sometimes they can increase eachother, but in healthy conditions, they become more inversely correlated.
  • Lowers the perceived cost of doing tasks. Higher-effort tasks for higher rewards.

Addiction #

‘High dopamine’ is anti-addiction. A lack of dopamine or an excess of serotonin causes adhedonia. Specifically, excess serotonin with low dopamine contributes to impulsivity. R

  • Low dopamine makes one crave something, but once you get it, the boost in dopamine is rather minor. This promotes drug use, binging on sweets, and stuff like that. It obviously also promotes ADHD/ADD and reduces learning/cognition. It’s the unexpected rewards that cause a surge in dopamine. R

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