Studies on the pharmacology of addiction focus on the properties of addictive drugs as they interact with the brain and on potential drug treatments for addiction. Some of this research overlaps with genetic research, as, for example, in studies using knock-out mice. The use of noninvasive brain imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) allows researchers to watch how the brain responds to doses of a drug.

Researchers at Harvard used fMRI to study how the brain responds as a person experiences a dose of cocaine. This novel technique opens up a new area of potential research.

We are now able to watch what happens to the brain during the various phases of drug use. Different parts of the brain were activated during these phases. For example, the cortex and limbic system were activated during the initial “rush,” but at times, when subjects reported feelings of craving, the nucleus accumbens was activated. The nucleus accumbens is part of the pleasure center of the brain that has been implicated in the reinforcing properties of addictive drugs.

Another study of cocaine involved the use of knock-out mice which lacked genes responsible for the movement of serotonin and dopamine in and out of cells. It was previously thought that these neurotransmitters were responsible for the addictive activation of the pleasure center of the brain. But the mice continued to show a preference for cocaine. What this study indicates is that there is a broader and more complex reaction to cocaine that underlies its addictive qualities.

PET scanning was recently used to compare the reinforcing effects of stimulants in people with low and high levels of dopamine D2 receptors, which are involved in the experience of euphoria when a person is using amphetamines. People with low D2 levels were more likely to experience euphoria with a dose of an amphetamine. People with high D2 levels tended to dislike the stimulant effect. This study increases our understanding of why some people are more likely than others to become addicted to amphetamines.

Electrical self-stimulation of the brain’s pleasure center and rates of self-administration by laboratory animals are commonly used to study the addictive potential of various drugs.

In this paradigm, electrodes that stimulate the brain’s pleasure center when activated are placed in the animal’s brain. Using the electrical self-stimulation paradigm, Athina Markou and colleagues at the Scripps Institute in La Jolla, California, measured the rate of electrical self-stimulation in rats before and after cessation of nicotine use. The rats were stabilized on nicotine doses equivalent to those of a typical smoker.

After the nicotine was stopped, the rats needed a substantial increase in the intensity of the electrical stimulation. This finding suggests that nicotine withdrawal is associated with a decrease in the brain’s ability to feel pleasure. Similar results occur during withdrawal from other addictive drugs.

The ability to pinpoint the site in the brain responsible for the unpleasant symptoms of withdrawal could lead to more effective drug therapy.

Currently, few medications are effective in treating addiction, and that is a major focus of research. As we learn more about the molecular mechanisms involved in addiction, the development of new drugs becomes possible. At present, most drugs being studied for use in addiction are those that have already been developed for another purpose.