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02-02-2007, 03:11 AM
“News from the Frontier”
Reprinted from BrainWork, Vol. 14 No. 1 January-February 2004
Why Only Some Become Addicted
Although it may seem obvious that not everyone who drinks becomes an alcoholic, the reason for that difference is anything but obvious. Now, as scientists become more familiar with the biochemistry of both healthy and addicted brains, they are beginning to tease out some of the differences between people who become addicted and those who do not.
At the opening public lecture, Nora Volkow, M.D., Director of the National Institute on Drug Abuse, described her recent work on the biochemical differences between individuals’ brains that may lead one person down the path of addiction while allowing another to sidestep the trouble.
“Drugs themselves are not sufficient to cause addiction,” Volkow says. A person’s environment and genes also influence the likelihood a person will become addicted. With that view in mind, her team has been looking for a biochemical factor that could predispose someone to addiction, something that would be affected by a wide variety of addictive drugs, not just one or two. One protein that fits that description is the dopamine receptor. Dopamine is one of the major neurotransmitters in the brain and is involved in pathways that sense pleasure and reward. The dopamine receptor, D2, lies on the far side of neural synapses in the brain and binds dopamine as it is released by the presynaptic neuron; binding of dopamine by the receptor transmits the electrical activation of one neuron to the next. But when Volkow’s team used a brain imaging technique called positron emission tomography (PET), which enables them to detect the level of a specific molecule such as the D2 receptor, they saw substantial differences between addicts and nonaddicts. Addicts generally have less D2 in their brains than do healthy controls. Interestingly, though, there is overlap, suggesting that D2 levels are not an absolute indicator of addiction. The levels of D2 appear to play a role in addiction, but are not sufficient to cause it, says Volkow.
The level of D2 plays an important role in how someone senses reward or value for a stimulus. At normal levels of D2, most people will feel a sense of pleasure - 2 - or reward from food, social interaction, or sex. If the level of D2 is too low, however, then this sense of reward (or salience, as the scientists term it,) wouldn’t occur in response to such natural stimuli.
Addictive drugs, however, increase the amount of dopamine that is released in the synapse relative to natural stimuli. These unusually high levels of dopamine make up for the lower levels of D2 receptor and induce a sense of salience for the addict, salience they may feel only when they take the drug because other stimuli do not induce adequate stimulation of the dopamine system. To test this model, Volkow asked healthy, nonaddicted people to participate in a study. In the first part of the experiment the researchers determined the level of D2 receptor in each participant’s brain via PET imaging. The volunteers were then given a nonaddictive drug that activates dopaminergic neurons. Half of the subjects liked how it felt and half thought it was unpleasant. When the researchers compared each participant’s emotional response to the drug with his or her level of D2, they found a strong correlation: The people with lower levels of D2 liked the drug, those with higher levels did not.
Volkow says the natural variation in D2 levels in the population may be important for who becomes an addict. For those people with higher D2 levels, the drug stimulus was so strong that they felt uncomfortable and would not be inclined to try it again, but for those with a lower receptor level, the drug created a pleasant sensation.
These data, though interesting, show correlation, not causation, so the team turned to animal studies where they can actively alter the levels of D2 receptor in an animal’s brain and look at the effects. In this study mice were given access to alcohol, which they could drink as they desired. The team then injected a gene into the animals’ brains that encodes the D2 receptor. With this gene delivery system, the amount of D2 in the brain increases 50 percent four days after injection, and by day 10 the level has dropped back to normal. The investigators reinjected the animals on day 20, and again by day 30 levels were normal.
“We see a dramatic change in alcohol consumption,” says Volkow: The 50 percent increase in D2 resulted in a 70 percent drop in alcohol consumption by the animals. “An increase in the D2 receptor has a profound effect on the pattern of alcohol consumption.” Volkow says that this and other work is beginning to draw a picture of why some people become addicted while others do not, and of what happens when they do. Such research, Volkow says, may enable clinicians not only to treat addiction but to prevent it.
Rabiya S. Tuma
© The Dana Press, 2004
Reprinted from BrainWork, Vol. 14 No. 1 January-February 2004
Why Only Some Become Addicted
Although it may seem obvious that not everyone who drinks becomes an alcoholic, the reason for that difference is anything but obvious. Now, as scientists become more familiar with the biochemistry of both healthy and addicted brains, they are beginning to tease out some of the differences between people who become addicted and those who do not.
At the opening public lecture, Nora Volkow, M.D., Director of the National Institute on Drug Abuse, described her recent work on the biochemical differences between individuals’ brains that may lead one person down the path of addiction while allowing another to sidestep the trouble.
“Drugs themselves are not sufficient to cause addiction,” Volkow says. A person’s environment and genes also influence the likelihood a person will become addicted. With that view in mind, her team has been looking for a biochemical factor that could predispose someone to addiction, something that would be affected by a wide variety of addictive drugs, not just one or two. One protein that fits that description is the dopamine receptor. Dopamine is one of the major neurotransmitters in the brain and is involved in pathways that sense pleasure and reward. The dopamine receptor, D2, lies on the far side of neural synapses in the brain and binds dopamine as it is released by the presynaptic neuron; binding of dopamine by the receptor transmits the electrical activation of one neuron to the next. But when Volkow’s team used a brain imaging technique called positron emission tomography (PET), which enables them to detect the level of a specific molecule such as the D2 receptor, they saw substantial differences between addicts and nonaddicts. Addicts generally have less D2 in their brains than do healthy controls. Interestingly, though, there is overlap, suggesting that D2 levels are not an absolute indicator of addiction. The levels of D2 appear to play a role in addiction, but are not sufficient to cause it, says Volkow.
The level of D2 plays an important role in how someone senses reward or value for a stimulus. At normal levels of D2, most people will feel a sense of pleasure - 2 - or reward from food, social interaction, or sex. If the level of D2 is too low, however, then this sense of reward (or salience, as the scientists term it,) wouldn’t occur in response to such natural stimuli.
Addictive drugs, however, increase the amount of dopamine that is released in the synapse relative to natural stimuli. These unusually high levels of dopamine make up for the lower levels of D2 receptor and induce a sense of salience for the addict, salience they may feel only when they take the drug because other stimuli do not induce adequate stimulation of the dopamine system. To test this model, Volkow asked healthy, nonaddicted people to participate in a study. In the first part of the experiment the researchers determined the level of D2 receptor in each participant’s brain via PET imaging. The volunteers were then given a nonaddictive drug that activates dopaminergic neurons. Half of the subjects liked how it felt and half thought it was unpleasant. When the researchers compared each participant’s emotional response to the drug with his or her level of D2, they found a strong correlation: The people with lower levels of D2 liked the drug, those with higher levels did not.
Volkow says the natural variation in D2 levels in the population may be important for who becomes an addict. For those people with higher D2 levels, the drug stimulus was so strong that they felt uncomfortable and would not be inclined to try it again, but for those with a lower receptor level, the drug created a pleasant sensation.
These data, though interesting, show correlation, not causation, so the team turned to animal studies where they can actively alter the levels of D2 receptor in an animal’s brain and look at the effects. In this study mice were given access to alcohol, which they could drink as they desired. The team then injected a gene into the animals’ brains that encodes the D2 receptor. With this gene delivery system, the amount of D2 in the brain increases 50 percent four days after injection, and by day 10 the level has dropped back to normal. The investigators reinjected the animals on day 20, and again by day 30 levels were normal.
“We see a dramatic change in alcohol consumption,” says Volkow: The 50 percent increase in D2 resulted in a 70 percent drop in alcohol consumption by the animals. “An increase in the D2 receptor has a profound effect on the pattern of alcohol consumption.” Volkow says that this and other work is beginning to draw a picture of why some people become addicted while others do not, and of what happens when they do. Such research, Volkow says, may enable clinicians not only to treat addiction but to prevent it.
Rabiya S. Tuma
© The Dana Press, 2004