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Thread: Dopamine: Dopamine Pathways; Agonists and Antagonists

  1. #11
    Veteran Member Petros Agapetos's Avatar
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    The mesolimbic pathway connects the Ventral Tegmental Area (VTA) in the midbrain to the nucleus accumbens.

    The nucleus accumbens (NAcc) is the "reward centre" of the brain.

    Each hemisphere has its own nucleus accumbens. As a whole, the nucleus accumbens has a significant role in the cognitive processing of motivation, aversion, reward (i.e., incentive salience, pleasure, and positive reinforcement), and reinforcement learning. Different NAcc subregions (core vs shell) and neuron subpopulations within each region (D1-type vs D2-type medium spiny neurons) are responsible for different cognitive functions.

    The Use of Antipsychotics and The Mesolimbic Pathway:

    All antipsychotics - regardless of whether they are antagonists or partial agonists - reduce dopaminergic neuro-transmission in the mesolimbic pathway, tuning it down via occupancy of D2 receptors. Partial agonist antipsychotics also have the ability to reduce mesolimbic neurotransmission. Otherwise they would not work as antipsychotics.

    As a result Antipsychotics can cause
    a lack of motivation,
    anhedonia (lack of pleasure),
    loss of drive and initiative,
    emotional suppression,
    affective blunting/flattening,
    etc.

    Atypical Antipsychotics
    are better than the typicals at targeting not just positive symptoms but also negative and cognitive symptoms of schizophrenia/psychosis.

    Partial Agonists (a variety of Atypical Antipsychotics) such as Abilify, Vraylar, and Rexulti have the ability to increase dopaminergic tone (D2) in regions of the brain deficient in dopamine, in addition to lowering dopamine (D2) activity where it is in excess. Antipsychotics do not really treat negative nor cognitive symptoms of schizophrenia. In order to treat them, one would need to activate D1 receptors in the mesocortical pathway. Antipsychotics whose affinity for D1 receptors is high and are antagonist can cause negative and cognitive symptoms or worsen them. Most atypical antipsychotics do not block D1 receptors by very much.
    Last edited by Petros Agapetos; 02-23-2019 at 12:45 AM.

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    Junior Member Elwy's Avatar
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    Opiates bind to opiate receptors in the nucleus accumbens and send signals to nearby dopamine terminals, instructing them to release more dopamine. The theory is that the activated receptor inhibits the release of GABA, which inhibits dopamine release, therefore increasing dopamine release.

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