Dopamine Determines Impulsive Behavior

No, really?  (Wonders if they should do a study on the post WLS communty – and then pass out the drugs.)

Brain scans illuminate the internal connection among the neurotransmitter, impulsiveness and addiction

Scientific American

Binge-shoppers and serial daters might perpetually be living at the whim of their latest impulse, and now research is getting to the biological basis of their seemingly random behavior. Impulsivity has long been linked to the neurotransmitter dopamine, which is involved in learning and reward. And a new model helps to illuminate the connection between the two. The work is described in a study published online July 29 in Science.

A team of researchers led by Joshua Buckholtz, a PhD candidate in neuroscience at Vanderbilt University, proposed that people who were more impulsive might have less active dopamine receptors in their midbrain but their brains would be more likely to fire off large quantities of the neurotransmitter when stimulated.

To verify their hypothesis, the researchers used PET scans to watch the brains of 32 healthy and psychiatrically normal test subjects ages 18 to 35 (who had no history of substance abuse) while they were taking a classic test to measure impulsivity. Before the first testing round, subjects had taken a placebo pill, but before the second, they were given an oral dose of amphetamine, which can stimulate the brain's reward pathways, mobilizing dopamine.

People who had the higher impulsivity scores had the lowest activity in the midbrain D2/D3 autoreceptors, which are in charge of receiving dopamine. But under the influence of the amphetamine, these impulsive individuals released much more dopamine than those who were less impulsive.

To see how these changes might be related to substance abuse—which has also been linked to dopamine abnormalities—the researchers polled the subjects about how much they wanted more of the amphetamine after the experiment ended.

"The people who had the highest levels of dopamine release reported subjectively stronger cravings after we gave them the drug," Buckholtz says. These findings "suggest a neurobiological link between human impulsiveness and drug abuse vulnerability," the researchers noted in their paper.

But what causes these individual differences? "Our best guess is that perhaps there's some inherited or environmentally mediated predisposition to having lower midbrain dopamine autoreceptor availability," Buckholtz says.

The evidence for genetic inheritance is strong, and another recent study, published earlier this month in Psychological Science, found people with a certain dopamine receptor type—known as DRD4—had different drinking habits than those without it. Specifically, test subjects with this variant were more likely to drink heavily if they had seen others doing the same while those without that variant kept their drinking moderate even when surrounded by heavier boozers.

The new results also suggest the potential for pharmacological interventions, Buckholtz notes. Some drugs for psychiatric conditions related to dopamine dysfunction, such as schizophrenia, work in broad strokes with "kind of a sledgehammer approach," he explains. Homing in on particular receptors and firing patterns might help develop drugs that could modulate in a "more targeted and perhaps nuanced way," he says, helping people with a broad range of dopamine-related ailments.

"Individuals vary widely in their capacity to deliberate on the potential consequences of their choices before they act," note the authors of a new study on the impulsive tendency. "Highly impulsive people frequently make rash, destructive decisions."

The study –

Dopaminergic Network Differences in Human Impulsivity

Joshua W. Buckholtz,1,2,*,{dagger} Michael T. Treadway,1,{dagger} Ronald L. Cowan,3,4 Neil D. Woodward,3,4 Rui Li,5 M. Sib Ansari,5 Ronald M. Baldwin,5 Ashley N. Schwartzman,1 Evan S. Shelby,1 Clarence E. Smith,3 Robert M. Kessler,5 David H. Zald1,3

Dopamine (DA) has long been implicated in impulsivity, but the precise mechanisms linking human variability in DA signaling to differences in impulsive traits remain largely unknown. By using a dual-scan positron emission tomography approach in healthy human volunteers with amphetamine and the D2/D3 ligand [18F]fallypride, we found that higher levels of trait impulsivity were predicted by diminished midbrain D2/D3 autoreceptor binding and greater amphetamine-induced DA release in the striatum, which was in turn associated with stimulant craving. Path analysis confirmed that the impact of decreased midbrain D2/D3 autoreceptor availability on trait impulsivity is mediated in part through its effect on stimulated striatal DA release.


1 Department of Psychology, Vanderbilt University, Nashville, TN 37240, USA.
2 Neuroscience Graduate Program, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37240, USA.
3 Department of Psychiatry, Vanderbilt University, Nashville, TN 37240, USA.
4 Psychiatric Neuroimaging Program, Vanderbilt University, Nashville, TN 37240, USA.
5 Department of Radiology, Vanderbilt University, Nashville, TN 37240, USA.
{dagger} These authors contributed equally to this work.

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