Dopamine

Not simply the 'pleasure chemical': dopamine drives movement, motivation and learning from surprises. Its pathways, the reward-prediction-error discovery, and its role in Parkinson's disease, addiction and schizophrenia.

Dopamine is made by a few hundred thousand neurons clustered in the midbrain — a tiny fraction of the brain's neurons — whose axons branch widely. Until the late 1950s it was thought to be just a stepping-stone in making noradrenaline. The Swedish pharmacologist Arvid Carlsson showed that it was a transmitter in its own right: rabbits given the drug reserpine, which depletes monoamines, became immobile, and they recovered when given L-dopa, which the brain turns into dopamine. He shared the 2000 Nobel Prize.

Four main pathways

The nigrostriatal pathway runs from the substantia nigra to the striatum and is essential for movement. The mesolimbic pathway from the ventral tegmental area (VTA) to the nucleus accumbens is central to motivation and reward. The mesocortical pathway, from the VTA to the prefrontal cortex, influences working memory and attention. The tuberoinfundibular pathway controls the hormone prolactin from the pituitary.

Surprise, not pleasure

In the 1990s Wolfram Schultz recorded dopamine neurons in monkeys. They fired a burst when an unexpected reward, such as juice, arrived. Once the monkey learned a light predicted the juice, the neurons fired at the light instead — and not at the expected juice. If the juice failed to come, their firing dipped. Dopamine was signalling a reward prediction error: "better than expected", "as expected" or "worse than expected". The same error signal is used to train artificial agents in reinforcement learning.

Kent Berridge's work further suggests dopamine is more about wanting (motivation to seek something) than liking (the pleasure of getting it).

When dopamine goes wrong

Loss of nigrostriatal dopamine neurons causes the movement problems of Parkinson's disease. Many addictive drugs raise dopamine strongly in the reward pathway. Excess dopamine activity in certain pathways is linked to psychosis, and most antipsychotic drugs block dopamine D2 receptors. ADHD medications increase dopamine and noradrenaline signalling.