Dopamine

Dopamine

Dopamine (DA) is a neurotransmitter. It is synthesised (created) within tyrosine neurons, and is the precursor to (it turns into these when synthesised) epinephrine and norepinephrine.

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Receptors

DA works by binding to one of the DA receptors, D1 to D5. These receptors are G-Protein coupled, meaning they bind to G-proteins in cell membranes, rather than activating ion channels directly. This binding changes levels of the enzyme adenylate cyclase (has a regulatory role in most cells), and that causes cAMP levels to increase (affecting cation channels).

Dopamine Pathways

Functions of Dopamine

Initiation and Control of Movement

We move to approach things we want, and to avoid things we don't want.

Dopamine antagonists can cause movement abnormalities (tardive dyskinesia (slow onset uncontrollable movements), for instance.

Reward

Dopamine is released in response to naturally rewarding stimuli (sex, drugs, rock and roll, food). (Radhakishum et al, 1988; Zernig et al, 1997).

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Approaching Reward Stimuli

Toxoplasma Gondii affects dopamine levels in infected rats caused them to become attracted to cat odor (useful for the parasite). (Vyas et al, 2007).

I.e. it creates behaviour that causes the rodent to approach a rewarding stimuli.

Aversive Surprising Events

DA is also release in response to salient, non-reward events; Budygin et al, 2012, found that DA is released in response to tail pinches in rats.

Learning and Surprise

Dopamine is released when a surprising event occurs; e.g. monkeys learning that flashes of light precedes juice.

  • Top: Surprising event of juice = increase in DA
  • Middle: Surprising event of light flash = increase in DA, Not surprising event of juice = no DA
  • Bottom: Surprising event of light flash = DA, Surprising event of no juice = decrease in DA

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Surprise

Dopamine has many functions, one surprisingly one is that it signals for surprise. It signals for error in predicted world state (positive for better state, negative for worse state).

Dopamine and Psychosis

Psychosis refers to an abnormal mental condition (losing touch with reality). There is much evidence that dopamine plays a role in psychosis (seen below), but why it does this involves linking biology and psychology. This is also below

Evidence

Anti-Psychotics

Dopamine plays a role in psychosis. All effective anti-psychotic medications block dopamine receptors. Seeman et al (1976) found evidence that the therapeutic dosage of these drugs is inversely proportional to the drug's binding affinity for D2 receptors.

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Dopamine Agonists

Dopamine agonists (e.g. methamphetamine) increase the levels of DA activation in the brain, and produce symptoms similar to the psychotic symptoms characteristic of Schizophrenia (Bell, 1973 - gave 16 addicts large doses of meth and 12 developed paranoid psychosis).

This happens with medicated DA-agonist drugs, as well as recreational drugs. Treating Parkinson's with L-DOPA (precursor to DA to increase DA synthesis) commonly causes psychotic symptoms (Fenelon et al, 2000).

Increased Synthesis in Psychotic Patients

Psychotic patients show heightened synthesis of dopamine in the striatum and prefrontal cortex (normally dopamine gets to the striatum via the nigrostriatal pathway, rather than being produced there).

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Explanation

If we consider psychosis to be a state of aberrant salience (errorful attention grabbing events). When the DA system is hyperactive (hence the psychosis), normally neutral things in the external world become super salient, and hence become internally significant.

Psychosis could then be considered the "aberrant assignment of salience to external objects and internal representations" (Kapur, 2003).

Aberrant Salience to Self-Generated Actions

  • Normal patients can't tickle themselves; they respond better to experimenter-generated tickling.
  • However, psychotic individuals can tickle themselves. Delusions of control might mean that self-generated actions are infused with abnormal salience.
  • Perhaps delusions of thought insertion can be explained by thoughts having unusual salience and hence being perceived as externally generated.