Dopamine Pathways in the Brain (and schizophrenia)

There are 4 main dopamine pathways in the brain:

  1. Nigro-Striatal: substantial nigra to basal ganglia, involved in movement (what gets affected to cause EPS: tardive dyskinesia, akatisia)
  2. Meso-Limbic: VTA to nucleus accumbens, “reward” pathway (causes the positive symptoms of schizophrenia)
  3. Meso-Cortical: VTA to cortex, motivation and emotional response (thought to cause the negative symptoms of schizophrenia)
  4. Tubulo-Infundibular: hypothalamus to posterior pituitary (hypoprolactinemia in untreated individuals, but D2 blockade with antipsychotics can cause a hyperprolactenemia)


Antipsychotic medication can be divided into 2 classes

  1. Typical/First Generation
  2. Atypical/Second Generation

Typicals are characterized by strong D2 antagonism in the mess-limbic and meso-cortical pathways. This can also lead to significant extrapyramidal symptoms (EPS). They also have strong CYP-450 metabolism (which means lots of interactions with other drugs and grapefruits).

  • High-potency typicals: only slightly anticholinergic & minimally sedating but have more weight gain and a higher risk of EPS
  • Low-potency typicals: more quite sedating and more anticholinergic (bradycardia, GI upset) but have a lower risk of EPS

Atypicals have less risk for EPS, but carry a higher risk for metabolic side-effects and weight gain. While they bind to D2 receptors (like typicals), atypicals have higher affinity for serotonin (5HT) receptors.

Clozapine is a little different from the other atypicals in that is has been shown to have a shorter half-life, which is thought to be why it doesn’t produce as many EPS. However it has the very specific (and serious) risk of agranulocytosis.

7 thoughts on “Dopamine Pathways in the Brain (and schizophrenia)

  1. Ali- these are amazing! I just happened across the dopamine pathways to review for a lecture- SUPER HELPFUL! I’m going to finish studying for step 3 on your site because I can actually focus on it. Thank you!!

    • I’m so happy that you find the doodles helpful! Spread the word, and if there are any topics you want to see, please let me know!

      • Hello Ali, I made the exact same sketches in my notes, so Im really excited to find yours.
        Do you think you could do some on the mania pathways?
        Thank you.

        • Thanks for your comment and sorry for the delay, I was out of the country with no Internet access! Right now is a very busy time for me, but hopefully in the future I’ll be able to add some of the mania pathways!

  2. Short and sweet explanation, it could be more magnificient if you have added the images of brain showing the dopaminergic pathway

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