Vol. 7, No. 4, 2001 Page 1&3
Strong evidence that genes play a part in alcoholism, and that gene therapy may some day be an effective treatment for alcoholics, comes from a study of "hard-drinking" rats.
Research shows that alcohol and other addictive drugs increase the brain's production of dopamine, a neurotransmitter linked to pleasure. Over time, however, heavy drinking depletes the D2 dopamine receptors that respond to the neurotransmitter. Scientists theorize that some individuals are prone to alcoholism due to a paucity of D2 receptors, and the further depletion that occurs after chronic drinking.
To investigate the effects of D2 receptor function on alcohol intake, Panayotis Thanos and colleagues used a harmless virus to transport the D2 receptor gene directly into the brains of rats. Using a radiotracer, they determined that levels of D2 receptors increased in these rats, peaking three to four days after the gene was injected and returning to baseline after eight days.
Next, the researchers studied rats divided into two groups: those that preferred alcohol to water when given the choice, and those that had no preference. In each group, some rats were injected with the D2 gene, while others received a placebo injection. Thanos et al. found that alcohol-preferring rats injected with the D2 gene reduced their preference for alcohol over water by 43 percent, and drank 64 percent less alcohol, than the placebo-treated rats. (Rats who initially showed little craving for alcohol also significantly reduced their intake of, and preference for, alcohol.) The effects wore off after eight days, when D2 receptor levels dropped to pre-treatment levels.
Thanos says the study provides the first evidence that high levels of D2 receptors may help protect against alcohol abuse. "This is a preliminary study," he says, "but when you see a rat that chooses to drink 80 to 90 percent of its daily fluid as alcohol, and then three days later it's down to 20 percent, that's a dramatic drop in alcohol intake—a very clear change in behavior. This gives us great hope that we can refine this treatment for future clinical use."
"Gene therapy reduces drinking in 'alcoholic' rats," press release, Brookhaven National Laboratory, September 9, 2001.
"Overexpression of dopamine D2 receptors reduces alcohol self- administration," P. K. Thanos, N. D. Volkow, P. Freimuth, H. Umegaki, H. Ikari, G. Roth, D. K. Ingram, and R. Hitzemann, Journal of Neurochemistry, Vol. 78, No. 5, September 2001, 1094-103. Address: Panayotis Thanos, Department of Medicine, Brookhaven National Laboratory, Upton, NY 11973.