Fewer dopamine receptors makes for risky business 

It seems preposterous that thrill seeker James Bond would have too few of anything, but new research suggests he may have a deficit of dopamine receptors.

Earlier work has suggested that a propensity for risky behaviors, like driving fast cars, gambling and drinking, is influenced by dopamine, one of the brain’s chemical messengers. Now a team of researchers led by neuroscientist David Zald has confirmed in humans a link between “novelty-seeking personality traits” and dopamine receptors. The team’s results appear in the Dec. 31 Journal of Neuroscience.

“Risk seeking is a basic characteristic that varies widely among people,” says Zald, of Vanderbilt University in Nashville. Of risk seekers, Zald says: “They get bored quickly with the same old, same old and turn to things like drug use, whiskey and sex. These exciting things have a lot of pull for them.”

Nerve cells excrete and detect dopamine to communicate with the rest of the brain. The chemical controls diverse brain functions — motor control, sleep and pleasure have all been linked to dopamine signaling. A nerve cell detects dopamine released from other nerve cells or from itself through proteins on the outside of the cell called dopamine receptors, which come in many varieties.

Many of the first experiments linking dopamine and thrill seeking were in rodents. The brains of novelty-seeking rodents — so named because the rats and mice spend more time exploring a new environment than do their complacent littermates — are less able to regulate the amount of dopamine in the brain. But equating a rodent sniffing around a new home to a person engaging in high-risk behavior like cocaine use is a stretch, the researchers point out.

To get a better idea about dopamine regulation in thrill-seeking humans, Zald’s team asked 34 healthy adult men and women a battery of questions to determine whether the people were prone to engage in risky behavior. Among other things, the subjects were asked whether they enjoy exploring new situations, make decisions rashly, buy expensive things and feel unconstrained by rules. The higher the score on the novelty-seeking scale, the greater the drive for novelty — which often leads to risky behavior.

Using PET, or positron emission tomography, to scan the volunteers’ brains, the researchers could track the location of an injected chemical that binds to two kinds of dopamine receptors, D2 and D3. The tracer signaled the presence of the dopamine receptors. Subjects who scored higher on the novelty-seeking scale had significantly fewer dopamine receptors in the ventral midbrain region.

Marcus Munafò of the University of Bristol in England calls the new research “very interesting” and says that such studies will lead to a better understanding of individual differences in temperament, which may explain why some people are more prone to engage in destructive behaviors.

When some receptors bind dopamine, they prevent the cells they reside on from releasing more of the chemical in what’s called a negative feedback loop. Since risky people have fewer of these dopamine-dampening receptors, they have fewer checks on dopamine levels. “When stimulated, high novelty seekers release more dopamine, and get a greater reinforcement,” says Zald.

Although this study offers an intriguing explanation for how different brains reward risk taking, Munafò points to an unanswered question. “Something this study can’t tell us is how these differences between high and low novelty-seeking individuals arise. They may be due to inherited differences, or developmental differences, or even due to the effects of living a novelty-seeking lifestyle. We’ll need more research to answer these questions.”