Volume 12, Number 1
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."
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
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
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
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
"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. 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
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
"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: firstname.lastname@example.org
From NIDA NOTES, January/February, 1997
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