News and Publications
Year In Review - 2000
Floyd E. Bloom, M.D., Chairman
uring the past year, the research strategy of the Department of Neuropharmacology has remained fundamentally unchanged. Our scientists continue to focus on the ways in which infectious, environmental, and genetic influences lead to psychiatric, neurologic, or endocrine brain disorders. Only by studying these underlying mechanisms can researchers ever hope to devise effective treatments for these diseases.
The efforts of the departmental faculty are concentrated into five broad areas: molecular, cellular and systems neuropharmacology; neurovirology; neuroimmunology; psychopharmacology; and clinical neuropsychopharmacology. The common arc of these areas is their impact on two major human health problems: substance abuse -- alcohol, psychostimulants, opiates, marijuana, and tobacco--and the effect of HIV infection on the central nervous system. With the appointment this year of Tamas Bartfai, Ph.D., and his colleagues in the Harold L. Dorris Center for Neurological Research, the work has been expanded into the field of neuropsychiatry.
This year's Nobel Prize in medicine was presented for research on signal transduction in the nervous system -- how neurons speak to each other through chemical messengers in the brain. The primary work of the department resides in this area. Scientists here study the mechanisms of neuron synaptic communication to determine the difference between what is considered normal neuronal signaling and how it differs in AIDS patients or those who are dependent on alcohol, cocaine or morphine. The studies of these altered or damaged synapses will help to better define the nature of these diseases, and eventually lead to a better understanding of how to normalize the condition.
While HIV doesn't directly affect neurons, the disease causes great difficulty for patients' attention and memory. Our work shows that these problems are the direct result of the inflammation brought on by the lymphocytes coursing through the brain. This inflammation interferes with neuron signaling, slowing down the processes within the cerebral cortex, the thinking part of the brain. It is this critical area of cognition that is affected most significantly and very early on in the infection. Research in the department, particularly that of Howard Fox, M.D., Ph.D., has been instrumental in increasing understanding how HIV interferes with neuronal signaling. Using computers to monitor the brain's response to sights and sounds, scientists recognize that these pathways are affected in the early stages of the infection and are developing methodologies to reverse them with aggressive treatment.
The chemical communication between neurons is also significantly disrupted by drug use, but in different ways from that of HIV infection. Drugs such as cocaine and morphine act as natural neural transmitters, turning on what is known as the reward system within the brain. The neurotransmitters reward positive behavior by making us feel good afterwards -- these are called reward circuits. A drug like cocaine simulates the actions of the reward circuits -- and dependence develops because of these internal rewards, leading to repeated drug use.
In working with the neurobiology of drug and alcohol dependence, George Koob, Ph.D., and his colleagues have demonstrated the long-term effects of alcohol on the brain. Identifying the nature of the neuron transmitters that these drugs act on makes it possible to design new therapies that interrupt those effects, and blunt the influence of the drug.
Scientists in the department have great hope that their fundamental research into the neuropharmacology of diseases like AIDS and substance abuse will one day help produce new medications and new approaches to alleviating human brain diseases. They can look back on a year of substantial progress in that fight, and continue to move forward into a new year full of opportunities.
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