Center Line Newsletter

Volume 18, Number 3, September 2007

Director's Column

Dr. Fulton T. Crews
Director, Bowles Center for Alcohol Studies

        Peptide neurotransmitters are clearly at the core of addiction. For many years, we have known that opiate peptides play a role in regulating sensations of reward and good feelings. Now we know that anti-opiate drugs such as naltrexone, an opiate receptor antagonist, are useful in reducing craving for alcohol and helping maintain abstinence. There are many more peptides that are major factors in alcohol dependence. Peptides are key to regulating anxiety, mood, hunger and eating. They show great promise in improving our understanding of what goes wrong in addiction.
         Many of the peptides involved in alcoholism originate in neurons in the hypothalamus, a key brain region that controls major hormone cycles as well as regulating feeding behavior. Neurons in the hypothalamus make peptides and send them across the brain via axonal projections. These peptides regulate initiation of eating and satiety, an important signal to stop consumption through processes that overlap with the drive to drink. Likely these drives are shifted to “hunger” for alcohol (craving) that is learned and then associated with environmental events like the evening, “I need a drink” response that many have after work.
         One exciting opportunity in our field is to discover how altering peptide responses might help people reduce consumption or stop drinking. Currently there are no approved drugs that antagonize Neuropeptide Y (NPY) or corticotropin releasing factor (CRF), although there are ongoing clinical trials with some experimental compounds. In the absence of a portfolio of peptide antagonists, Todd Thiele has brilliantly used transgenic mice with modified peptide signaling to further establish the role of these peptides in alcohol drinking behavior. These studies require arduous breeding and other controls to avoid the traps of transgenic mice studies. Dr. Thiele has elegantly established that key peptides control drinking behavior. His studies are leading the field in understanding what peptides in brain are regulating drinking. NPY and CRF are among the most important.
         We recently found decreased NPY in alcoholic human brain, consistent with increased drinking behavior in mice that have decreased NPY expression. These studies provide a foundation for pharmaceutical development of drugs that could test his hypotheses and maybe someday help the afflicted to stop drinking and regain control of their lives. With scientists like Todd Thiele, I know that further scientific progress will eventually bring these important findings to bear on the treatment of alcoholism.