Director’s Message
Wheeler Center

Drug addiction is a multifaceted problem that defies solution by any single-minded approach. Because drugs act directly on the brain and the brain is the origin of addictive behaviors, Wheeler Center scientists are dedicated to uncovering the changes that lead to addictive behavior.

One of the most important facts about addiction is that most addicting substances produce similar changes in the brain pathways that underlie reinforcement and motivation. This means that any drug, be it alcohol, tobacco, heroin or psychostimulants like cocaine and amphetamine, can be a gateway to addiction.

On the other hand, because most people who are exposed to drugs do not become addicts an important research question is why some people are resistant while others are vulnerable. Genetics undoubtedly plays a key role in determining these individual differences and a number of Wheeler Center scientists are studying the genetics of addictive behaviors.

As a society, we have tried a variety of approaches to reduce drug use. So far, little progress has been made. For example, we have tried reducing the supply by going after growers, manufacturers, smugglers, wholesalers and dealers. This approach has failed, in part because gateway substances like alcohol and tobacco are legal and readily available. When interdiction of supply has ‘succeeded’, the major impact has been that the addict switches to a different drug. The commonality of neurobiological action among different drugs suggests that only a broad-based approach, aimed at the individual addict and the addictive process, is likely to have a major impact on the scope of the problem. The one clear success story is the reduction in cigarette use that was accomplished by establishing the health risks of smoking, educating the public so that they largely want to quit, passing laws that reduce smoking in public areas, increasing the price through taxation and, finally, providing pharmacological aids for treating abstinence (nicotine chewing gum and patches). Peer pressure and behavioral modification have also helped reduce tobacco smoking. The key first step is convincing individuals that their habit is actually harmful to themselves and those close to them, in order to motivate them to break their pattern of addiction.

The specific focus of research at the Wheeler Center is to find pharmacological aids for individuals who want to quit taking drugs but who are unable to do so. We believe that the best strategy for achieving this goal is to understand how the drugs produce the brain changes that result in drug or alcohol craving. When this is accomplished, the next step is to target those mechanisms in the most selective manner possible in order to develop safe and effective treatments.

The Wheeler Center is well positioned to make major contributions to the development of new treatments for addiction. Our greatest strength lies in the large number of excellent neuroscientists at the University of California San Francisco. Our Neuroscience Program is in the very top tier of universities nationwide This reputation for excellence acts as a magnet for recruiting outstanding new faculty and graduate students. These talented people will be the source of new ideas and new scientific techniques. One of the core brain processes in addiction is learning. Thus better understanding of learning is essential to solving the biology of addiction. Many UCSF neuroscientists, both within and outside the Wheeler Center, are working on this problem.

Not only do we have the talent, but I believe that the breadth of learning research at UCSF enhances the likelihood of scientific breakthroughs. Each approach is necessary but each by itself is insufficient for a full explanation of addiction. For example, we know what morphine and cocaine do at the molecular and cellular level, but we do not yet understand how those molecular changes are translated into the altered behavior that defines addiction. At the behavioral level we know that an abstinent rat is more likely to self-administer cocaine when placed in the room where he has received cocaine in the past. How does the molecular action of the drug interact with environmental sensory cues in such a way that the drug related cues become powerful motivators for addictive behaviors? The only way to find out is by studying the relevant nerve cells while the animal is learning or exhibiting the addictive behaviors. By virtue of the collaborative culture of UCSF in general and the Wheeler Center in particular, different investigators bring molecular, behavioral, genetic, anatomical and physiological approaches to the same table. The resulting experiments are at once more rigorous and more relevant to the problem of addiction. This culture creates a situation where we make each other’s experiments better and accelerate progress toward our goal of improving treatment through better understanding of the brain mechanisms underlying addiction.

Howard Fields, MD, PhD

A Message From the Director