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Dopamine Primer

How dopamine makes us human.

For human beings, dopamine is kind of where it's at. Overall levels and the left-brain versus right-brain amounts of dopamine are major distinguishing factors between our brains and those of our primate cousins. Dopamine may well be part of what makes us human—meaning awfully bright, able to plan ahead, and resist impulses when necessary.

What is dopamine? It's a neurotransmitter, which means it controls communication in the brain. Dopamine can tell a neuron to fire off a signal or not, and modulates the signals. Dopamine is ancient—found in lizard brains and every other animal along the evolutionary tree up to homo sapiens. But humans have a great deal of dopamine, and over many generations it seems we have evolved to have more and more.

Control where dopamine ends up in the brain isn't just determined by straight up mendelian genetics. As I discussed in this post, our prenatal neurochemical environment had a lot to do with how our dopamine machinery migrates and works in our brains. Which brings up an important point—one special thing about humans is our bipedalism. Being upright while mom is pregnant exposes our fetal brains to different environments than other primates, so the theory is this elevated the dopamine levels in the left hemisphere of most people's brains compared to other primates. I know. Go with it for a minute. It's just a theory.

Humans also eat a lot of meat and fish compared to other primates—meat and fish give us more dopamine precursors. More dopamine is also associated with both greater competitiveness, aggression, and impulse control—one could see how that particular combination of traits would be selected for over human evolution.

Serotonin, another neurotransmitter, is our oldest neurotransmitter and the original antioxidant—dopamine is what made humans so successful.

Now the biochemistry. Dopamine is a type of neurotransmitter called a catecholamine. Catecholamines have, not surprisingly, a catechol chemical group attached to an amine.

How do we get dopamine? We eat it. The precursor amino acid from the protein we eat is called tyrosine. Tyrosine becomes dopa via the enzyme tyrosine hydroxylase, and dopa becomes dopamine via the actions of dopa decarboxylase. (One more chemical reaction can turn dopamine into its best buddy neurotransmitter, norepinephrine, but more on that later). As is the case with serotonin and its precursor tryptophan, tyrosine can cross the blood brain barrier, but dopamine itself cannot. That means that the dopamine our brain needs must be manufactured from dopamine machinery and precursors in the brain.

Still with me? What happens without dopamine, or with screwy dopamine machinery or inefficient dopamine? Well, in development this lack can cause mental retardation, which is the case in a rare genetic disease called PKU and cretinism (a type of mental retardation caused by iodine deficiency). Dopamine problems are implicated in ADHD, Alzheimer's, Parkinson's, depression, bipolar disorders, binge eating, addiction, gambling, and schizophrenia.

Having too much dopamine in the wrong place can make you psychotic. Illicit drugs that dump loads of dopamine (or strongly inhibit its reuptake, which is similar to dumping loads of dopamine) include cocaine and methamphetamines. Therefore high amounts of dopamine can cause euphoria, aggression and intense sexual feelings.

We need dopamine in the right place at the right time in the right amounts. When it all comes together, we are the awesomest ape around. Dopamine will motivate us, and it is the driving neurotransmitter in competitive behaviors. When our dopamine machinery isn't working properly, problems ensue (not surprisingly). Dopamine is linked to everything interesting about metabolism, evolution, and the brain.

As I mentioned in the first paragraph, dopamine is distributed quite differently on the different sides of the human brain, and is is speculated that this lateralization is responsible for how very human we are. The left brain (in almost all right-handed and most left-handed people) is responsible for language, linear reasoning, mathematics, that sort of thing, whereas the right side is usually responsible for intuition, holistic reasoning, some elements of music and speech intonation, etc.

It's funny, really, how different the sides of the brain are. They look much the same. My right and left lungs look a little different, but they have the same function. My right and left feet do pretty much the same thing. But remove my left brain, and I'll be an entirely different person. Amazingly, if one is young enough, half the brain can be scooped out and removed (if necessary, usually to control intractable seizures), leaving the child with pretty normal intellectual functioning (though motor functioning on one side is usually irrevocably lost). This finding (among others) led one prominent neuroscientist to pen a famous chapter called "Is Your Brain Really Necessary?"

The human brain has 100 billion neurons. Only 20,000 or so carry dopamine, and they do so in four major tracts (and some other minor ones we won't go into here). Keep in mind that the brain is a gorgeous and mysterious place with many wonderful names, like Rivendell or Brigadoon. The areas are named either anatomically (the dorsolateral prefrontal cortex) or because it reminded the anatomist of yore of some other important anatomical structure (the mammilary bodies). Or for some other obscure reason (the tegmentum? Oh, that's Latin for "covering." Okay!)

Dopamine is made in two little areas in the deep animal recesses of the brain—the substantia nigra and the ventral tegmental area. From these starting gates, the dopamine tracts reach out to various segments.

1) The nigrostriatal tract is important to neurologists. It brings dopamine from the substantia nigra to the striatum or "basal ganglia." These neurons are responsible for a lot of the motor control of the body. Death of dopaminergic neurons in the substantia nigra leads to the symptoms of Parkinson's disease—tremor, stiffness, loss of voluntary movement (though someone with advanced Parkinson's may not be able to toss a ball to you, if you toss a ball to him, he might be able to use different reflex motor brain tracts and catch it). This pathway is also affected in various choreas, such as the possibly wheat-related Huntington's Chorea.

2) The mesolimbic pathway goes from the ventral tegmental area to the limbic system. The limbic system of the brain controls reward and emotion, and includes the hippocampus and the medial frontal cortex. This is the pathway that is thought to be responsible for addiction and psychosis.

3) The mesocortical pathway goes from the ventral tegmental area to the dorsolateral frontal cortex. This is the pathway responsible for planning, responsibility, prioritizing, motivation, and some elements of emotional response. This is one of the damaged areas in ADHD and depression.

4) The tuberoinfundibular pathway has my favorite name (though not as fun an anatomical name as the as the anterior inferior thoracoacromial artery). It's a dopamine pathway between the hypothalamus and the pituitary gland, and the most important part is that dopamine inhibits prolactin release. So blocking dopamine means prolactin increases, enabling breastfeeding and whatnot. (Yup—prolactin is one of the hormones responsible for lactation! I love it when the names make sense like that).

Having fun yet? In psychiatric terms, the mesolimbic and mesocortical pathways are by far the most important. They have a lot to do with how we behave, and who we are. There, we are done! The hard part is over! We'll have some real fun with speculation about the differences between men and women and psychiatric illness and personality disorders in the very next post. Stay tuned!

The major source for this article is The Dopaminergic Mind in Human Evolution and History by Fred Previc.

Copyright Emily Deans, M.D.

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