and Human Services (HHS)
EXPIRED
NONHUMAN PRIMATE MODELS OF NEUROBIOLOGICAL MECHANISMS OF ADOLESCENT ALCOHOL
ABUSE AND ALCOHOLISM
Release Date: October 4, 2001
RFA: RFA-AA-02-006
National Institute on Alcohol Abuse and Alcoholism
(http://www.niaaa.nih.gov/)
Letter of Intent Receipt Date: January 21, 2002
Application Receipt Date: February 19, 2002
THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. MODULAR
INSTRUCTIONS MUST BE USED FOR RESEARCH GRANT APPLICATIONS REQUESTING LESS
THAN $250,000 PER YEAR IN ALL YEARS. MODULAR BUDGET INSTRUCTIONS ARE PROVIDED
IN SECTION C OF THE PHS 398 (REVISION 5/2001) AVAILABLE AT
http://grants.nih.gov/grants/funding/phs398/phs398.html.
PURPOSE
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) invites
applications using nonhuman primate models to focus on the following areas:
1) neurobiological mechanisms and risk factors for alcoholism during late
childhood through adolescence, 2) the relative contribution and/or
interaction of genetic, environmental, and social factors (e.g., stress, peer
influences) with neurobiological mechanisms in the development of adolescent
alcohol abuse, 3) evaluation of the immediate and long-term consequences of
heavy drinking during adolescence on cognitive/brain functioning, and 4) the
contribution of early alcohol exposure (juvenile and adolescent periods) to
excessive drinking and abnormal cognitive and social functioning during
subsequent developmental stages. It is the intent of this Request for
Applications (RFA) to foster interdisciplinary research (e.g., behavior,
neuroanatomy, neurophysiology, neuropharmacology, neuroimaging). Therefore,
good integration among components with diverse scientific disciplines is
essential. NIAAA strongly encourages investigators with expertise in primate
developmental biology and behavior to seek collaborations with established
alcohol researchers in order to elucidate the neurobiological mechanisms of
adolescent alcohol abuse and alcoholism. A high priority will be given to
applications that include integrated research.
HEALTHY PEOPLE 2010
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2010," a PHS-
led national activity for setting priority areas. This Request for
Applications (RFA), Title of RFA, is related to one or more of the priority
areas. Potential applicants may obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople/.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments, and eligible
agencies of the Federal government. Racial/ethnic minority individuals,
women, and persons with disabilities are encouraged to apply as Principal
Investigators.
MECHANISM OF SUPPORT
This RFA will use the National Institutes of Health (NIH) research project
grant (R01) and the NIAAA exploratory/developmental (R21) award mechanism.
Responsibility for the planning, direction, and execution of the proposed
project will be solely that of the applicant. The total project period for a
research project grant (R01) application submitted in response to this RFA
may not exceed 5 years. Exploratory/developmental grants (R21) are limited to
3 years for up to $100,000/year for direct costs. (See Program Announcement
PA- 99-131, NIAAA Exploratory/Developmental Grant Program,
http://grants.nih.gov/grants/guide/pa-files/PA-99-131.html, for a complete
description of the R21 mechanism.)
Applicants are also encouraged to submit applications for Investigator-
Initiated Interactive Research Project Grants (IRPG) which is available at
http://grants.nih.gov/grants/guide/pa-files/PA-96-001.html. The IRPG
mechanism requires the coordinated submission of related research project
grants (R01) from investigators who wish to collaborate on research, but do
not require extensive shared physical resources. These applications must
share a common theme and describe the objectives and scientific importance of
the interchange of, for example, ideas, data, and materials among the
collaborating investigators. A minimum of two independent investigators with
related research objectives may submit concurrent, collaborative, cross-
referenced individual R01 applications. Applicants may be from one or
several institutions.
This RFA is a one-time solicitation. Future unsolicited competing
continuation applications will compete with all investigator-initiated
applications and be reviewed according to the customary peer review
procedures. The anticipated award date is September 29, 2002.
FUNDS AVAILABLE
The NIAAA intends to commit approximately $2.5 million in FY 2002 to fund
approximately 6 to 8 new and/or competitive continuation grants in response
to this RFA. Because the nature and scope of the research proposed may vary,
it is anticipated that the size of each award will also vary. Although the
financial plans of the NIAAA provide support for this program, awards
pursuant to this RFA are contingent upon the availability of funds and the
receipt of a sufficient number of meritorious applications. At this time, it
is not known if this RFA will be reissued.
RESEARCH OBJECTIVES
Background
Although NIAAA recently launched a basic research initiative on adolescence,
relatively few studies to date define the neurobiological mechanisms and
consequences of heavy drinking in adolescents. One reason for the paucity of
research in this area is the difficulty of studying the neurobiological and
physiological (e.g., endocrine, heart rate, neurophysiology) mechanisms of
alcohol abuse or dependence in human adolescents, in part, due to ethical and
legal considerations, that prohibit administering alcohol to youths. Most of
the controlled laboratory studies on the neurobiological and behavioral
mechanisms of adolescent drinking have been conducted in rodents. However,
there are several reasons that nonhuman primate models may be more
advantageous for evaluating the etiology and consequences of adolescent
alcoholism and for investigating cross-generational phenomena. First,
nonhuman primates are genetically more similar to humans than rodents, with
some species sharing between 90 to 99% of their DNA with humans. Because of
the significant genetic overlap, many of the physiologic systems in nonhuman
primates are highly similar to humans in terms of patterns of development and
vulnerability to environmental influences including alcohol exposure (1).
Second, the adolescent period in laboratory rodents is very brief (for males,
about three weeks to a month and for females, about two weeks). Behavioral
paradigms and social/environmental manipulations used in adult rodent studies
may require weeks or even months of training, periods that extend well beyond
the rodent adolescent window. Nonhuman primate models are a better approach
because of their extended adolescent period (2-4 years or longer in some
species) and complex behavioral repertoires and social systems. Furthermore,
because of their protracted lifespan, it is possible to perform more
extensive and elaborate studies on alcohol exposure during the adolescent
period and determine the long-term consequences of this early exposure. For
these reasons, NIAAA proposes an initiative to focus on neurobiological
mechanisms of adolescent alcohol abuse and dependence, neurobiological and
physiological risk factors for development of alcoholism, and consequences of
excessive drinking in adolescents using nonhuman primate models.
1. Characteristics of Normal Adolescent Development
During the period of late childhood and adolescence, development of
neurobiologic systems is incomplete. Although final brain size and available
neurons are largely fixed early in infancy, plasticity of the brain continues
during adolescence through the processes of overproduction and elimination of
synapses, progressive myelination, variation in the evolution of
neurotransmitter systems, and changes in the rate of brain electrical and
metabolic activity (2). In addition, hormonal levels change dramatically
during adolescence as a result of the onset of puberty. The first change
indicative of puberty is the secretion of adrenal androgens and neuroactive
steroids. After a prolonged period of suppression during the childhood/
juvenile period, there is reactivation of the hormonal regulatory systems
that control reproduction (3). This reinstatement stimulates the release of
gonadal hormones (e.g., testosterone in males and estrogen in females).
Pulsatile release of growth hormones also increases during the growth spurt
of adolescence.
Corresponding to the shifts in brain and hormonal status are significant
transitions in cognitive, psychological, and social development. Adolescence
is marked by the emergence of new thinking skills, reassessment of body
image, focus on peer relationships, and a desire to establish self-identity
and distance from parents. Sensation seeking and risk taking behaviors also
increase relative in adolescence to other ages, which is consistent with the
need to establish new social relationships, explore novel domains, and
achieve parental independence. Thus, environmental influences during
adolescence, including alcohol consumption per se, may interact with unique
neurobiological and physiological strengths and weaknesses to predispose or
protect an individual from alcohol abuse and/or dependence. A better
understanding of alcohol"s effects during adolescence on the complicated
interaction among neurobiologic, genetic, psychosocial and environmental
factors could lead to earlier and more effective prevention and treatment
strategies.
2. Neural and Behavioral Changes Unique to Adolescence
Evidence from human, nonhuman primate, and rodent studies indicates that
unique neuroanatomical, neurochemical and behavioral changes are occurring
during postnatal development, including adolescence. The prefrontal cortex
(PFC), an area thought to mediate higher cognitive abilities, undergoes major
changes during adolescence in humans and other animals (4). Absolute volume
of the PFC declines during adolescence, and connectivity of the PFC and other
cortical regions are substantially refined through preferential synapse
elimination. At the same time that loss of excitatory input to the PFC is
occurring through synpatic pruning, dopaminergic and cholinergic inputs to
the PFC increase during adolescence relative to other developmental stages.
In addition, several neurochemical markers in the cortico-mesolimbic dopamine
system experience reorganization during adolescence, suggesting possible
shifts in the relative balance of dopamine activity between the PFC and
subcortical structures in the mesolimbic system. For example, D1 and D2
receptors show overproduction and decline at puberty in the striatum and
nucleus accumbens.(5) Basal dopamine synthesis and turnover in the striatum
and nucleus accumbens are lower in early adolescence than in late
adolescence, whereas the converse is true in PFC. Finally, maturational
changes occur in other limbic regions (hippocampus and amygdala) and
neurotransmitters systems during adolescence (6).
During the 7- to 10-day period just prior to the onset of puberty, referred
to as "periadolescence," both male and female rats are behaviorally and
pharmacologically distinct from younger and older animals. Periadolescent
animals are more "hyperactive" as measured by tests of exploratory behavior
and social play, and have difficulty with complex discrimination learning
tasks (7). Pharmacologically, periadolescent animals are less responsive
(hyposensitive) to the stimulatory effects of catecholaminergic agonists, but
more sensitive to the dopamine antagonist haloperidol, a pattern suggestive
of functional immaturity of dopamine autoreceptors, or postsynaptic dopamine
receptors, in mesolimbic brain regions. Dopamine is one of many
neurotransmitters in the cortico-mesolimbic reward system that have been
implicated in the alcohol addiction process. However, whether periadolescent
animals drink more alcohol than early postpubertal or adult rats because of
an immature dopaminergic system, are more susceptible to alcohol dependence,
or fail to attain mature dopamine function following high early intakes are
important research questions that need to be explored.
Nonhuman primates also undergo major social and behavioral changes during
adolescence that distinguish this stage of development. While females remain
in their natal troop at the onset of puberty, males typically leave their
troop and join all-male gangs before entering a new troop. This adolescent
emigration period is especially risky for males, since they engage in
substantial amounts of aggressive behavior with peers and competitive adults.
They are also subjected to predation and possible malnourishment as they
explore new environments and emigrate to new territory (1,6). Data exists
regarding behavioral changes and synaptic pruning of various neurotransmitter
receptors in primate cortex during adolescence. However, less normative data
is available on other neurochemical and pharmacological aspects of nonhuman
primate neurodevelopment and their interaction with cognitive and social
development.
Given the relatively prolonged adolescent period in nonhuman primates, an
understanding of the ontogeny of psychopharmacological responsiveness in
neurotransmitter systems related to mechanisms of alcohol reinforcement, or
alcohol"s subjective effects using primate models could be extremely
important in understanding the development of alcoholism during adolescence.
3. Current Research on Neurobiological and Behavioral Mechanisms of
Adolescent Drinking
Predisposition to Alcoholism: Neurobehavioral research in human adolescents
has largely been limited to studies of vulnerability in children who are at
high risk because of a positive family history of alcoholism. These
investigations suggest that there are neurocognitive and neurophysiological
abnormalities in children of recovering alcoholics that could be early
indicators of risk for alcoholism. Recently, it was found that high risk
children of alcoholics show reduced right amygdala volumes, an area
responsible for emotional processing (8). More important, the
neurophysiological and neuroanatomical abnormalities may be most pronounced
during the prepubertal and late adolescent years. This latter finding
underscores the importance of considering developmental stages, particularly
adolescence, when trying to identify early risk markers for alcoholism.
Animal studies have found functional differences in the dopamine system
between the selectively bred alcohol-preferring and nonpreferring lines of
rats as early as 28 days of age (9). Given that the divergent drinking
characteristics of these lines are also evident at this age, it is possible
that hyposensitivity of the dopamine system may be a potential biological
marker for susceptibility to alcohol abuse.
Rhesus monkeys with low serotonin metabolite (5-HIAA) levels in cerebrospinal
fluid and greater availability of serotonin transporters are more aggressive
and exhibit less intoxication on initial exposure to alcohol (10). This
pattern of behavioral and biochemical markers is similar to those
predisposing to early onset alcoholism in humans, and may be related to early
developmental stress (see below). It would be important to determine the
relationship among environmental factors, genetic backgrounds, and
neurobiological and behavioral markers in predisposing to alcoholism using
primate models.
Ontogeny of Response and Tolerance to Alcohol: Adolescent rats consume higher
absolute levels of alcohol than older animals, possibly due to their relative
insensitivity to the sedating and motor impairing effects of ethanol (6).
The relative insensitivity of young rats to ethanol is seen not only with
ethanol-induced sleep time and motor performance, but also with ethanol-
induced hypothermia. This invulnerability, which occurs despite slower rates
of ethanol metabolism in younger animals, is due to a lower initial brain
sensitivity to ethanol, and to accentuated development of acute and chronic
tolerance early in life. Although research in nonhuman primates suggests
that low sensitivity to alcohol may be present in this species as well, more
research is needed on neurobiological mechanisms for the ontogenetic
differences in alcohol sensitivity.
Behavioral and Physiological Consequences of Early Drinking: While decreased
sensitivity to the sedative effects of alcohol may enable greater intakes in
adolescents, this increased exposure to alcohol could have harmful effects.
Investigators have found that inhibition by ethanol of hippocampal NMDA-
mediated synaptic potentials and long-term potentiation is greater in
adolescents than adults (11). Behaviorally, adolescent rats show greater
impairment on acquisition of a spatial memory task after ethanol exposure,
and binge alcohol exposure in rats during adolescence produces long-lasting
changes in memory function (12). Furthermore, chronic ethanol treatment may
lead to increased N-methyl-D-aspartate (NMDA)-mediated neurotoxicity, which
could be exacerbated by repeated withdrawals such as during binge drinking.
Consistent with this hypothesis is the finding that severity of alcohol and
drug withdrawal symptoms may be a powerful marker of neuropsychological
impairments in detoxified late adolescents and young adults (13).
Furthermore, a recent study found reduced hippocampal volumes in adolescents
with a history of alcohol abuse/dependence disorder (14). Juvenile animals
exposed to heavy binge-like episodes of ethanol develop damage in the frontal
olfactory cortex and limbic system structures, including the hippocampus
(15). The immature brain is more susceptible to NMDA neurotoxicity and since
teenagers are more likely to engage in weekend binge drinking, it is
important to study the effects of chronic binge patterns of ethanol exposure
on brain structure, neurochemistry, and cognitive functioning. Primate
models may be a better choice for studying the long-term consequences of
alcohol exposure because of the prolonged adolescent period, which allows
extensive manipulation of different types and length of exposure. This
coupled with the new neuroanatomical and neuroimaging techniques offers a
unique opportunity to study the brain changes associated with adolescent
drinking.
Stress, Hormones, Adolescence, and Alcohol Abuse: Late childhood and
adolescence are periods of extreme flux in terms of both sexual and
psychosocial development. The stress response system (hypothalamic-
pituitary-adrenal axis) develops between 5 and 9 years of age, resulting in
increased secretion of many adrenal steroids (cortisol, androstenedione,
dehydroepiando-sterone). This is followed by increased activity of
gonadotropins and then sex steroids (estradiol in females and testosterone in
males). Increased life stressors associated with sexual and social maturation
together with hormonally-induced mood and behavior changes could contribute
to increased consumption of alcohol during the adolescent period (16).
In adult humans and animals, the relationship among stress, drinking, and
underlying neuroendocrine or neurochemical mechanisms is complex. In
adolescents, a few studies using nonhuman primates have shown that under
conditions of social separation stress, subjects double their rates of
alcohol consumption (17,18). In these studies, individual differences in
stress-induced drinking are attributed to anxiety-like behaviors mediated by
ontogenetic changes in cortisol and corticotropin levels or to poor impulse
control and impaired social competence associated with reduced serotonin
functioning (a trait-like marker present in infancy).
With respect to sex steroid hormones, recent evidence from adult nonhuman
primates indicates that sensitivity to the subjective effects of ethanol
changes during different phases of the menstrual cycle due to alterations in
endogenous levels of ovarian-derived hormones (19). Given that adolescence
is a time when hormonal systems are still developing in humans and animals,
and may be fluctuating, research on the interaction among life stressors,
affective states, and hormonal changes may be critical to understanding the
onset and continuation of adolescent drinking.
Early Exposure as a Predictor of Later Alcohol Abuse. Early exposure to
alcohol at or before 14 years has been shown to be a powerful predictor of
later alcohol abuse and dependence. There are two possible explanations for
this effect. First, early alcohol use may simply be a marker, not a causative
factor, of later alcohol abuse. Second, it is possible that alcohol exposure
during adolescence may actually alter neurodevelopmental processes in such a
way that the likelihood of later abuse is increased. However, there have
been relatively few reports using animal models to study the effects of early
exposure to alcohol (including adolescence) on later alcohol consumption, and
the results have been conflicting. More studies are needed to explore
whether there is a causal relationship between early chronic exposure to
alcohol and later alcohol problems, as well as the underlying mechanisms for
this effect. Primates, because of their extended adolescent period, offer a
good opportunity to study this early exposure effect.
Research Areas of Interest
More basic research is needed using nonhuman primate models to elucidate the
neurobiological mechanisms of alcoholism and the effects of alcohol ingestion
throughout the juvenile/adolescent period. Nonhuman primate models would be
important to identify neurobiologic and behavioral risk factors for
alcoholism, the neural consequences of heavy drinking during adolescence, as
well as to determine the role of environmental factors such as stress in
enhancing the likelihood of early alcohol exposure and later intake. Primate
models will be important for investigating the neurochemical,
neuropharmacological, and behavioral mechanisms underlying the variable
response to alcohol during ontogeny with respect to alcohol sensitivity,
reinforcement, and discrimination. The complex social groups of advanced
nonhuman primates containing well-established relationships and
multigenerational lineage are conducive to interdisciplinary studies
incorporating genetic, neurobiological, and environmental factors. The
advent of PET and SPECT neuroimaging technologies and radioactive ligands
that label dopamine, opiate, and benzodiazepine receptors could allow
investigations of the functional ontogeny of various neurotransmitter systems
in adolescent primates, as well as the effects of early alcohol exposure on
development of these systems, and the relationship of these changes to future
drinking and social functioning.
Additional areas needing further research include, but are not limited to:
o Use of PET and SPECT neuroimaging in combination with behavioral measures
to identify risk markers for alcoholism, the ontogeny of neuroanatomical and
neurochemical circuits of intoxication and reinforcement, and to assess
progression of alcohol damage and recovery of function during abstinence.
o Ontogenetic studies to compare patterns of alcohol-related behaviors (e.g.,
alcohol reinforcement, sensitivity) and their neurochemical,
neuropharmacological, neurophysiological, and neuroanatomical mechanisms
during each stage of postnatal development through adulthood.
o Studies of the role of prefrontal cortex in alcohol-seeking behavior and
alcohol consumption during the adolescent period. Use of prefrontal
anatomy/circuitry, physiology, and pharmacology to study alcohol-induced
changes rewiring of synaptic connections and in cognitive functioning at
multiple levels of analysis from cellular responses to behavioral
functioning.
o Studies of gender differences in alcohol"s effect on normal hormonal
activation during puberty, mechanisms of alcohol"s effect on neuroendocrine-
neurotransmitter interactions, and the relationship among hormonal changes,
affective state, and stress on drinking during adolescence.
o Studies to examine the interaction among premorbid temperament/
personality, cognitive functioning, neurobiological, environmental, and
genetic factors in the development of addictive behaviors in adolescents.
SPECIAL REQUIREMENTS
This RFA is intended to publicize NIAAA’s interest in the use of primate
models of development in the study of neurobiological mechanisms of
adolescent drinking. Investigators wishing to obtain support for such
research who lack expertise in alcohol research should seek collaboration
with investigators experienced in alcohol research, insofar as such
experience will prove essential for proper study design and data analysis.
Investigators desiring to establish such collaborations are encouraged to
contact the individual mentioned under INQUIRIES, below. Awardees will be
expected to attend one joint meeting every two years in or near Washington,
DC, in order to review progress, and should include sufficient funds in their
budgets to support such attendance.
URLS IN NIH GRANT APPLICATIONS OR APPENDICES
All applications and proposals for NIH funding must be self-contained within
specified page limitations. Unless otherwise specified in an NIH
solicitation, internet addresses (URLs) should not be used to provide
information necessary to the review because reviewers are under no obligation
to view the Internet sites. Reviewers are cautioned that their anonymity may
be compromised when they directly access an Internet site.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT
The Office of Management and Budget (OMB) Circular A-110 has been revised to
provide public access to research data through the Freedom of Information Act
(FOIA) under some circumstances. Data that are (1) first produced in a
project that is supported in whole or in part with Federal funds and (2)
cited publicly and officially by a Federal agency in support of an action
that has the force and effect of law (i.e., a regulation) may be accessed
through FOIA. It is important for applicants to understand the basic scope
of this amendment. NIH has provided guidance at:
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm
Applicants may wish to place data collected under this RFA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the
application.
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that includes a
descriptive title of the proposed research, the name, address, and telephone
number of the Principal Investigator, the identities of other key personnel
and participating institutions, and the number and title of the RFA in
response to which the application may be submitted. Although a letter of
intent is not required, is not binding, and does not enter into the review of
a subsequent application, the information that it contains allows IC staff to
estimate the potential review workload and plan the review.
The letter of intent is to be sent to:
RFA-AA-02-006
Extramural Project Review Branch
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Room 409, MSC 7003
Bethesda, MD 20892-7003
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 443-4375 FAX: (301) 443-6077
by the letter of intent receipt date listed.
APPLICATION PROCEDURES
The PHS 398 research grant application instructions and forms (rev. 5/2001)
at http://grants.nih.gov/grants/funding/phs398/phs398.html are to be used in
applying for these grants. This version of the PHS 398 is available in an
interactive, searchable PDF format. Beginning January 10, 2002, however, the
NIH will return applications that are not submitted on the 5/2001 version.
For further assistance contact GrantsInfo, Telephone 301/710-0267, Email:
[email protected].
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS
The modular grant concept establishes specific modules in which direct costs may
be requested as well as a maximum level for requested budgets. Only limited
budgetary information is required under this approach. The just-in-time concept
allows applicants to submit certain information only when there is a possibility
for an award. It is anticipated that these changes will reduce the
administrative burden for the applicants, reviewers and NIH staff. The research
grant application form PHS 398 (rev. 5/2001) at
http://grants.nih.gov/grants/funding/phs398/phs398.html is to be used in
applying for these grants, with modular budget instructions provided in Section
C of the application instructions.
The RFA label available in the PHS 398 (rev. 5/2001) application form must be
affixed to the bottom of the face page of the application. Type the RFA
number on the label. Failure to use this label could result in delayed
processing of the application such that it may not reach the review committee
in time for review. In addition, the RFA title and number must be typed on
line 2 of the face page of the application form and the YES box must be
marked. The RFA label is also available at:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
Submit a signed, typewritten original of the application, including the
Checklist, and three signed, photocopies, in one package to:
CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)
At the time of submission, two additional copies of the application must be
sent to:
Chief, Extramural Project Review Branch
National Institute on Alcohol Abuse and Alcoholism
Willco Bldg, Suite 409
6000 Executive Blvd, MSC 7003
Bethesda, MD 20892-7003
Applications must be received by the application receipt date listed in the
heading of this RFA. If an application is received after that date, it will
be returned to the applicant without review.
The Center for Scientific Review (CSR) will not accept any application in
response to this RFA that is essentially the same as one currently pending
initial review, unless the applicant withdraws the pending application. The
CSR will not accept any application that is essentially the same as one
already reviewed. This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications must
include an introduction addressing the previous critique.
REVIEW CONSIDERATIONS
Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NIAAA. If the application is not responsive to the RFA,
CSR staff may contact the applicant to determine whether to return the
application to the applicant or submit it for review in competition with
unsolicited applications at the next review cycle.
Applications that are complete and responsive to the RFA will be evaluated
for scientific and technical merit by an appropriate peer review group
convened by the NIAAA in accordance with the review criteria stated below.
As part of the initial merit review, all applications will receive a written
critique and undergo a process in which only those applications deemed to
have the highest scientific merit, generally the top half of the applications
under review, will be discussed, assigned a priority score, and receive a
second level review by the NIAAA National Advisory Council or Board.
Review Criteria
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments reviewers will be asked to discuss the following aspects
of the application in order to judge the likelihood that the proposed
research will have a substantial impact on the pursuit of these goals. Each
of these criteria will be addressed and considered in assigning the overall
score, weighting them as appropriate for each application. Note that the
application does not need to be strong in all categories to be judged likely
to have major scientific impact and thus deserve a high priority score. For
example, an investigator may propose to carry out important work that by its
nature is not innovative but is essential to move a field forward.
(1) Significance: Does this study address an important problem? If the aims
of the application are achieved, how will scientific knowledge be advanced?
What will be the effect of these studies on the concepts or methods that
drive this field?
(2) Approach: Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics?
(3) Innovation: Does the project employ novel concepts, approaches or
method? Are the aims original and innovative? Does the project challenge
existing paradigms or develop new methodologies or technologies?
(4) Investigator: Is the investigator appropriately trained and well suited
to carry out this work? Is the work proposed appropriate to the experience
level of the principal investigator and other researchers (if any)? Will the
team of investigators and collaborators receive sufficient participation or
guidance from individuals with expertise in nonhuman primate/developmental
neurobiology/alcohol research.
(5) Environment: Does the scientific environment in which the work will be
done contribute to the probability of success? Do the proposed experiments
take advantage of unique features of the scientific environment or employ
useful collaborative arrangements? Is there evidence of institutional
support?
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
o The reasonableness of the proposed budget and duration in relation to the
proposed research.
o The adequacy of the proposed plan to share data, if appropriate.)
Schedule
Letter of Intent Receipt Date: January 21, 2002
Application Receipt Date: February 19, 2002
Peer Review Date: April-May 2002
Council Review: August 2002
Earliest Anticipated Start Date: September 29, 2002
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o scientific merit (as determined by peer review)
o availability of funds
o programmatic priorities.
INQUIRIES
Inquiries concerning this RFA are encouraged. The opportunity to clarify any
issues or answer questions from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Ellen D. Witt, Ph.D.
Neuroscience and Behavioral Research Branch
National Institute on Alcohol Abuse and Alcoholism
Willco Bldg., Suite 402
6000 Executive Blvd., MSC 7003
Bethesda, MD 20892-7003
Telephone: (301) 443-6545
FAX: (301) 594-0673
Email: [email protected]
Direct inquiries regarding fiscal matters to:
Ms. Judy Simons
Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Blvd, Suite 504, MCS 7003
Bethesda, MD 20892-7003
Telephone: (301) 443-2434
FAX (301) 443-3891
Email: [email protected] [email protected]
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance No.
93.273. Awards are made under authorization of Sections 301 and 405 of the
Public Health Service Act as amended (42 USC 241 and 284) and administered
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