Dopamine Genes and Addiction Predisposition
Researchers have identified five different dopamine receptors in the brain’s Reward System, several of which are implicated in addiction.
One genetic variation suspected to predispose people to addiction involves the gene that engineers the dopamine D2 receptor. Early addiction researchers found that alcoholics’ brains contained significantly fewer D2 receptors than normal drinkers. This suggested that alcohol abuse caused a defensive reaction to dopamine overstimulation: reducing the number of receptors to dock with dopamine. Shrinking the number of receptors renders the reward system less efficient, blunting the overstimulation. This is the classic explanation of tolerance.
However, later studies demonstrated that this D2 mutation wasn’t only caused by drug abuse, it could be inherited: it was found in rats who hadn’t been given any drugs.1
Subsequently. people were also found to have been born with this D2 mutation. Dr. Ernest P. Noble, a professor at UCLA, says they experience life less intensely because their neurons are innately under-stimulated. They self-medicate to compensate, he says.2 In a direct echo of all the “born addict” stories heard at AA meetings, Dr. Noble says they describe their first drug-taking experience as filling a hole they’d always felt. They often reported the first time they felt normal was after their first drink or drug, he said.3
Conversely, a genetic variation which elevates the numbers of D2 receptors provides protection against addiction even for those at high risk from other factors. Researchers found that a high-risk-of-addiction group who had a family history of alcoholism but hadn’t become alcoholics themselves, had 10% more D2 receptors than their low-risk counterparts, which compensated for their higher risk.4
Genes associated with dopamine D1 and D3 receptors have also been tied to addiction in animal models.
“Teenage” rabbits who were exposed to cocaine while in utero had altered dopamine D1 receptors. Although the number of D1 receptors was the same as a control group, the location of the D1 receptors was abnormal: these D1 receptors were “sequestered” inside the cells rather than on the cells’ surface, which interfered with their normal function. Behaviorally, this resulted in attention problems and insensitivity to stimulants, like amphetamines.1
In another study, a drug which acts as a D3 antagonist (which binds to D3 receptors so dopamine can’t), was administered in rats bred to seek alcohol. The rats reduced their drinking significantly.2
So, genetic predisposition plays a significant role in who becomes addicted to drugs and who doesn’t.
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1. Addiction Breakthrough May Lead to New Treatments, medicalnewstoday.com, March 3, 2007.
2. Genetic Studies Promise a Better Path to Treatment of Addictions, New York Times, Nov. 14, 2000.
3. Genetic Studies Promise a Better Path to Treatment of Addictions, New York Times, Nov. 14, 2000.
4. Clues to Brain’’s Protective Mechanisms Against Alcoholism; medicalnewstoday.com, Sep. 6, 2006.
5. Prenatal Cocaine’s Lasting Cellular Effects; medicalnewstoday.com, Jan. 16, 2007.
6. Two Studies Offer Clues About How Alcoholic Behavior Is “Switched” On, Brookhaven National Laboratory Press Release, May 9, 2005.