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National Institute on Drug Abuse -  NIDA NOTES
News
Volume 12, Number 1
January/February 1997

NIDA Fosters Next Generation of Neuroscience Researchers With Mentored Awards


By Michael D. Mueller
NIDA NOTES Staff Writer

NIDA is helping to prepare the next generation of drug abuse researchers through fellowships, training grants, and mentored research career development awards designed for scientists who show special promise in addiction studies. In recent years, the Institute has expanded its support for the mentored awards, giving special emphasis to attracting clinicians to drug abuse research.

"The mentored awards are one of the most important mechanisms that NIDA has to bring scientists early in their careers, especially clinicians, into addiction research," says Dr. Timothy P. Condon, NIDA's associate director for science policy, who oversees the Institute's research training and career development activity. "We must keep training investigators who have broad and varied expertise if we are to solve the problem of drug abuse, and these awards, the K01 and K08, enable us to attract some of the most promising talent available."


 Award

Recipients of NIDA's mentored research career development awards took part in a special session at the annual Society for Neuroscience meeting last fall that showcased the awards program and featured their neuroscience research. With the reward recipients are NIDA Deputy Director Richard A. Millstein, bottom left, and featured speaker Dr. Floyd Bloom, editor of Science magazine and past president of the Society for Neuroscience, bottom right.


The mentored awards support scientists with clinical and/or doctoral degrees who have the potential to make significant contributions in drug abuse research. Awardees work with a leading researcher for up to 5 years, during which time they build and refine the skills needed for a research career.

The K01, formerly known as the K21, is the Mentored Research Scientist Development Award. It is used to support outstanding biological or behavioral scientists. An applicant must have a research doctoral degree such as a Ph.D. and 1 to 4 years of postdoctoral experience. The K08, formerly the K20, is the Mentored Clinical Scientist Development Award. This award is designed for clinicians who show great promise as researchers but need more research skills. An applicant must have an M.D. or other clinical degree, at least 2 years of clinical training, and minimal research experience.

"The K01 and K08 awards are particularly attractive because they come with a salary as well as money to support the awardee's research," says Dr. Condon. The mentored award salary ranges up to $75,000 per year.

The number of NIDA mentored awards has increased from 5 in 1991 to a projected estimate of up to 70 in 1997. The Institute's total support for the mentored awards rose from $500,000 in 1991 to an estimated $7.8 million in 1997.

NIDA's mentored award program was showcased at a special poster session titled "NIDA: The Next Generation" that was held this past fall at the Society for Neuroscience annual meeting in Washington, D.C. Most of the 21 presenters were K01 or K08 awardees. The featured speaker at the session was NIDA-funded researcher Dr. Floyd Bloom, past president of the Society for Neuroscience and editor of Science magazine.

Dr. Lynda Erinoff, formerly with NIDA's Division of Basic Research and currently with NIDA's Office on AIDS, coordinated the poster session. "Our intent was to tell the neuroscience research community about the availability of these awards and the kinds of research we are supporting, as well as to present some of the findings of the investigators who are pursuing exciting and innovative directions," says Dr. Erinoff.

The mentored awards are not limited to neuroscience research. They are available to investigators working in all areas of research supported by NIDA, including epidemiology, prevention, and treatment.

Currently, more than 64 researchers are receiving K01 or K08 awards from NIDA. The investigations being carried out across the Nation by these young scientists address a host of problems and issues central to drug use.

For example, Dr. Mark von Zastrow, an assistant professor in the Departments of Psychiatry and Cellular and Molecular Pharmacology at the University of California at San Francisco (UCSF), is studying the regulation of neurotransmitter receptors, or chemical messengers, located on the surface of nerve cells in the brain. Through these studies, Dr. von Zastrow and collaborating researchers at the University of California at Los Angeles (UCLA) have gained a greater understanding of the effects of morphine on opioid receptors, which are neurotransmitter receptors responsible for the pain-killing and addictive effects of morphine and similar opiate drugs.

Opioid receptors normally are activated by opioid peptides, a class of opioid substances that occur naturally in the body. Because morphine and other opiates bind to and activate these same receptors, they have been called "molecular mimics" of opioid peptides.

Under NIDA's K award, Dr. von Zastrow and his colleagues have found that opioid peptides cause opioid receptors to be removed from the surface of the brain's nerve cells and transmitted inside the cells, where they are inaccessible to other neurotransmitters or drugs. Morphine also activates opioid receptors, but it does not cause the receptors to be removed from the surface of nerve cells. Consequently, opioid receptors activated by morphine remain on the cell surface for long periods of time. This difference may be of great importance to understanding the biology of opiate action and addiction.

"Differences between the effects of opiate drugs and naturally occurring opioid peptides on this process show clearly that opiate drugs do not act simply as molecular mimics of the opioid peptides," says Dr. von Zastrow. "We hope that our studies will provide important new insight into the molecular actions of opiate drugs and how they cause tolerance and addiction by eluding the brain's normal regulating mechanisms," he says.

Dr. von Zastrow's mentors at UCSF are Dr. Keith Mostov, associate professor in the Departments of Anatomy and Biochemistry and Biophysics, and Dr. Paul Berger, assistant professor in the Department of Psychiatry. Collaborating researchers at UCLA include Dr. Chris Evans and Dr. Nicholas Brecha.

Dr. Delia Vazquez, a pediatric endocrinologist and research investigator in the Department of Psychiatry at the University of Michigan at Ann Arbor, is studying early development of brain circuits that regulate how animals and humans react to stress and how early stress can change these circuits. Specifically, she is studying the linkages that develop between the hippocampus, a part of the brain important to regulating and eventually shutting down the stress response, and the hypothalamus, a brain structure that releases hormones which activate stress pathways.


 Dr.

Dr. Howard Gutstein, a K-award recipient at the University of Michigan, explains the poster that details his research to NIDA Deputy Director Richard A. Millstein at the annual Society for Neuroscience meeting.


"Changes in brain circuits brought on by stress early in life can greatly influence how we respond to stress later on," says Dr. Vazquez. "These changes may make us more vulnerable or responsive to stressful experiences." According to Dr. Vazquez, animal studies show that early life stress has an impact on the quality of the stress response later in life, making animals more vulnerable to stress. The more vulnerable animals are to stress, the more likely they are to self-administer amphetamines and cocaine, she says. (See "Anxiety and Stress Found To Promote Cocaine Use in Rats," NIDA NOTES, September/October 1996, p. 6.) To bring the point closer to home, child abuse and neglect appear to increase the risk of later drug use and dependence, she says. Dr. Vazquez' mentors are Dr. Huda Akil and Dr. Stanley Watson, codirectors of the Mental Health Research Institute at the University of Michigan.

Dr. Howard Gutstein was a pediatric anesthesiologist in private practice in California before relocating to the University of Michigan at Ann Arbor to study the neurobiological basis of pain perception, particularly as it relates to chronic pain and how pain relievers affect pain perception circuits in the brain. He and his colleagues are mapping the activation of genes, known as immediate-early genes, that respond to stress and pain. These genes may help tell a person which stimuli are painful and which are stressful but not physically painful. Pain and stress differ in terms of which areas in the brain are activated over time. The investigators also are looking at how morphine affects the genes activated by stress and pain and whether or not chronic pain affects the development of narcotic tolerance.

"Our goal is to identify drugs that target pain perception neural circuits and relieve pain and suffering without causing the undesirable side effects we can encounter today with pain relievers," says Dr. Gutstein. Dr. Gutstein's mentors are Dr. Huda Akil and Dr. Stanley Watson, codirectors of the Mental Health Research Institute at the University of Michigan.

Dr. Lois Kehl of the Department of Restorative Sciences at the University of Minnesota School of Dentistry in Minneapolis is using her K award to find out whether opioids or similar agents can provide pain relief when administered locally-or directly at the site of acute or chronic pain-rather than when administered systemically in the form of a pill or an injection. Chronic myalgia, or muscle pain, is a common complaint that can sometimes result in addiction to narcotic analgesics, alcohol, or other painkillers. A positive finding in this study would suggest that small doses of locally administered opioids or other therapeutic drugs may help control pain while reducing the potential for drug dependence among patients experiencing chronic pain.


"The mentored awards are one of the most important mechanisms that NIDA has to bring scientists early in their careers, especially clinicians, into addiction research."


Dr. Kehl and her mentor, Dr. Kenneth Hargreaves, an associate professor in the Department of Restorative Sciences, have completed a preliminary study in which they investigated treatment of muscle pain in rats using a locally administered opiate analgesic. They now are designing a similar study involving humans that will examine the effectiveness of small doses of opiates administered locally to treat pain in the trapezius muscle of the upper shoulder.

"The bottom line is we are looking for better ways to treat acute and chronic muscle pain-effective pain relief with less risk of drug dependence," says Dr. Kehl.

Other K awardees include Dr. Hans Breiter, a psychiatrist working in the field of radiology at Massachusetts General Hospital's Department of Psychiatry, who is using neuroimaging to map the emotional circuitry of the human brain, and Dr. Linda Chang, at Harbor-UCLA Research and Educational Institute, who is applying neuroimaging to the study of cocaine users with HIV. (For more information, see "NIDA-Supported Researchers Use Brain Imaging to Deepen Understanding of Addiction," NIDA NOTES, November/December 1996, p. 12.) Dr. Athina Markou at the Scripps Research Institute in La Jolla, California, is studying the neurobiology of cocaine and nicotine reward. (For more information, see "NIDA-Funded Studies Shed Light on Neurobiology of Drug Craving," NIDA NOTES, May/June 1995, p. 5.)

Interested researchers can obtain a copy of the K01 or K08 announcement from either their institution's office of sponsored research or NIDA's home page on the World Wide Web on the Internet at http://www.nida.nih.gov/

For more information about NIDA's mentored career development awards program, contact Dr. Lucinda L. Miner, Deputy Research Training Coordinator, Office of Science Policy and Communications, NIDA, 6001 Executive Blvd, Bethesda, Maryland 20892. Internet address: cm171w@nih.gov


From NIDA NOTES, January/February, 1997


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