Full Text PA-97-034
NIH GUIDE, Volume 26, Number 4, February 7, 1997
PA NUMBER:  PA-97-034
P.T. 34


National Institute on Alcohol Abuse and Alcoholism
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is
seeking research grant applications to study the alcohol tobacco
interaction in its implications for alcoholism treatment.  The
objective of this program announcement is to encourage research that
will lead to improved strategies for treating alcohol and nicotine
dependence in patients receiving care for problem drinking.  Such
research may identify and test relevant clinical intervention
strategies; identify interactions between the two substances that
have implications for relapse prevention, or further understanding of
the alcoholism treatment process by investigating reinforcement
mechanisms underlying conjoint abuse of the two substances.
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This program
announcement is related to the priority areas of alcohol abuse
reduction and alcoholism treatment. Potential applicants may obtain a
copy of Healthy People 2000 (Full Report: Stock No. 017-001-00474-0,
or Summary Report:  Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington,
DC 20402-9325 (telephone 202-512-1800).
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.
Foreign institutions are not eligible for First Independent Research
Support and Transition (FIRST) (R29) Awards.  Regular research grant
applications (R01) from foreign institutions are limited to three
Research support may be obtained through applications for a regular
research grant (R01), FIRST Award (R29), or an
Exploratory/Developmental Grant (R21).  Applicants for R01s may
request support for up to five years.  In FY 1996, the average total
cost per year for new R01s funded by the NIAAA was approximately
$200,000.  Because the nature and scope of the research proposed in
response to this program announcement may vary, it is anticipated
that the size of an award will vary also.
FIRST (R29) Award applications must be for five years.  Total direct
costs for the five-year period may not exceed $350,000 or $100,000 in
any one budget period.  exploratory/developmental grants are limited
up to two years for up to $70,000 per year, for direct costs.  FIRST
Awards and Exploratory/Developmental Grants cannot be renewed, but
grantees may apply for R01 support to continue research on the same
topics.  Potential applicants for FIRST Awards or
Exploratory/Developmental Grants should obtain copies of the specific
announcement for these programs from the NIAAA Home Page
HTTP://NIAAA.NIH.GOV or from the program contacts listed under
Inquiries.  Program project grant applications (P01) will not be
accepted for this announcement.  Investigators who wish to submit an
application that requests more than $500,000 for direct costs in any
one year must contact program staff prior to submitting an
Applicants may submit applications for Investigator-Initiated
Interactive Research Project Grants (IRPG) (refer to PA-94-086, Vol.
23, No. 28, July 29, 1994).  Interactive Research Project Grants
require the coordinated submission of related research project grants
(R01), and to a limited extent, FIRST Award (R29) applications 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 and R29 applications.
Applicants may be from one or several institutions.  Further
information on these and other grant mechanisms may be obtained from
the program contacts listed under INQUIRIES.
Behavioral Research
During the past decade many lines of converging data have suggested
that alcohol and tobacco consumption are correlated.  For example,
smokers consume two times as much alcohol per capita as do
non-smokers (Carmody et al., 1985) and their risk of excessive
drinking is also twice that of non-smokers, a relationship that holds
across a broad range of demographic variables (Henningfield et al.,
1990; Johnson and Jennison, 1992).  Alcoholism itself is estimated as
10 to 14 times more prevalent among those who smoke than those who do
not (DiFranza and Guerrera, 1990).  In addition, heavy drinking tends
to be associated with heavy smoking with 85 percent of currently
drinking alcoholics smoking daily.  Although smoking has
substantially declined in the United States to approximately 30
percent of adults, it has diminished very little among alcoholics.
Co-occurrence of smoking and excessive drinking has important
treatment implications.  For example, previous or current problems
with alcohol and alcohol treatment bodes negatively for success in
smoking cessation (Bobo et al., 1987; DiFranza and Guerrera, 1990;
Sandor, 1991).  On the other hand, smoking cessation prior to formal
alcoholism treatment (Miller et al., 1983) appears to improve
subsequent drinking outcome.  Conversely, reducing drinking appears
to improve the prospects for successful smoking cessation (Burling et
al., 1982).  Curiously, participation in a stop-smoking program
conducted during the course of alcoholism treatment was found to
enhance maintenance of sobriety, even though the intervention had
little impact on smoking behavior itself (Burling et al., 1991).
Discontinuation of smoking and long-term abstinence from drinking are
also associated.  Alcoholics who maintain sobriety longer have been
reported as more successful in smoking cessation  (Bobo et al., 1987;
Hughes, 1993).  Similarly, relapse to drinking may prompt smoking
relapse (Shiffman et al., 1985; Sees and Clark, 1993).
Several pharmacologic and behavioral mechanisms have been proposed to
explain the association between smoking and drinking.  At a
pharmacologic level some degree of cross-tolerance seems to occur
between nicotine and alcohol as sympathetic nervous system agents,
each of which has both depressant and stimulant effects.  Second,
conjoint use of the two substances may also be due to accelerated
metabolism of one substance following ingestion of the other. Third,
nicotine and alcohol may somewhat counteract the aversive effects of
each other, while potentiating reinforcing effects.
Basic Science
Administration of both alcohol and nicotine together to laboratory
animals alters the responses to either drug when administered alone.
For example, prior exposure to a low dose of nicotine increases
alcohol consumption, whereas a high dose decreases consumption
(Gauvin, Morre and Holloway, 1993).  Animals respond more for lateral
hypothalamic stimulation after nicotine treatment and less after
ethanol treatment, compared to controls (Schaefer and Michael, 1992).
However, when both agents are given together, responding is higher
than after nicotine alone suggesting that alcohol is enhancing the
reinforcing properties of nicotine.  In discriminative stimulus
studies, nicotine enhances the alcohol-like effects of nicotine in
alcohol-preferring rats compared to non-preferring rats (Gordon,
Meehan and Schecter, 1993).
Further evidence of interactions between alcohol and nicotine derives
from comparative sensitivity and cross-tolerance studies suggesting
that the sensitivity to alcohol and nicotine appears related.  Mice
selectively bred for alcohol sensitivity are also more sensitive to
nicotine compared to alcohol-insensitive mice.  In addition,
alcohol-sensitive mice rendered tolerant to alcohol are also tolerant
to nicotine (de Fiebre and Collins, 1993; Luo, Marks and Collins,
1994 and Majchrzak and Dilsaver, 1992) and nicotine-tolerant,
alcohol-sensitive mice display cross-tolerance to alcohol (Collins et
al., 1993).  These effects are not observed in alcohol-insensitive
mice.  In other studies, nicotine can antagonize the motor
incoordinating effect of alcohol (Dar and Bowman, 1994), whereas a
nicotinic receptor antagonist partially blocks increased locomotor
activity induced by alcohol (Blomqvist, Soderpalm and Engel, 1992).
To better understand the treatment implications of alcohol and
tobacco co-dependence, it is necessary to determine the mechanism of
interaction of these two agents and how the actions are modified when
both drugs are co-administered.  Several lines of evidence suggest
that although alcohol and nicotine have different molecular
structures, they have actions in common.  For example, both
substances stimulate the release of dopamine in the nucleus
accumbens, (Imperato and Di Chiara, 1986a, 1986b), an area of the
brain involved with the reinforcing properties of drugs.  A role for
dopamine is also suggested by the observation that blockade of
dopamine receptors increases both alcohol and nicotine intake
(Gauvin, et al, 1993; Dawe et al, 1995).
Acetaldehyde is a pyrolysis product of tobacco and has been suggested
to play a role in the reinforcing effects of alcohol.  The rapid
transport of acetaldehyde in an unmetabolized and undiluted form from
the lungs through the heart to the brain may enhance the reinforcing
properties of smoking.
Areas of Research Interest
The following list of topics is intended only to illustrate NIAAA
interests; topics not specified should not be viewed as excluded from
consideration.  The primary objective of this program announcement is
to enhance the efficacy of treatment for nicotine addicted,
alcohol-dependent patients.  To that end, research studies are
solicited in the following areas.
Research is needed to determine the conditions under which tobacco
use serves as a salient risk factor for alcohol relapse.
Research suggests several hypothesized mechanisms for the linkage in
conjoint alcohol-tobacco use.  Studies are needed to more clearly
specify these putative mechanisms and understand their interactions.
Studies are needed which identify the optimal sequencing of alcohol
and smoking cessation in treatment programs.
Studies are needed which investigate the use of new/existing
pharmacologic agents as adjuncts to alcohol and smoking cessation and
in the maintenance of abstinence.
Research is needed which elucidates factors that underlie the joint
vulnerability to alcohol and nicotine dependence.
Research is needed to develop common assessment methodologies for
alcohol and tobacco dependence which will lead to improved treatment
Research is needed to determine the extent to which alcohol acts
through nicotinic receptors and other receptors and whether chronic
nicotine exposure can alter those actions.
Studies are needed which clarify the nature of the discriminative
stimuli for alcohol and nicotine and how these stimuli interact.
Studies are needed to determine whether conditioned cues associated
with smoking enhance alcohol reinforcement.
Studies are needed which assess the role of acetaldehyde in
alcohol-nicotine interactions.
It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This policy results from
the NIH Revitalization Act of 1993 (Section 492B of Public Law
All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH
Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994.
Applications are to be submitted on the grant application form PHS
398 (rev. 5/95) and will be accepted at the standard application
deadlines as indicated in the application kit.  Application kits are
available at most institutional offices of sponsored research and may
be obtained from the Division of Extramural Outreach and Information
Resources, National Institutes of Health, 6701 Rockledge Drive, MSC
7910, Bethesda, MD 20892-7910, telephone 301/710-0267, Email:
ASKNIH@odrockm1.od.nih.gov.  The title and number of the program
announcement must be typed in section 2 on the face page of the
Applications for the FIRST award (R29) must include at least three
sealed letters of reference attached to the face page of the original
application. FIRST award (R29) applications submitted without the
required number of reference letters will be considered incomplete
and will be returned without review.
The completed original application and five legible copies must be
sent or delivered to:
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817-7710 (for express/courier service)
Applications that are complete will be evaluated for scientific and
technical merit by an appropriate peer review group convened in
accordance with the standard NIH peer review procedures.  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 appropriate
national advisory council.
Review Criteria
Criteria to be used in the scientific and technical merit review of
alcohol research grant applications will include the following:
1.  The scientific, technical, or medical significance and
originality of the proposed research.
2.  The appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research.
3.  The adequacy of the qualifications (including level of education
and training) and relevant research experience of the principal
investigator and key research personnel.
4.  The availability of adequate facilities, general environment for
the conduct of the proposed research, other resources, and
collaborative arrangements necessary for the research.
5.  The reasonableness of budget estimates and duration in relation
to the proposed research.
6.  Adequacy of plans to include both genders and minorities and
their subgroups as appropriate for the scientific goals of the
research.  Plans for the recruitment and retention of subjects will
also be evaluated.
7.  Where applicable, the adequacy of procedures to protect or
minimize effects on human and animal subjects and the environment.
The review criteria for Exploratory/Developmental Grants (R21) and
FIRST Awards (R29) are contained in their program announcements.
Applications recommended for approval by the appropriate national
advisory council will be considered for funding on the basis of the
overall scientific and technical merit of the proposal as determined
by peer review, programmatic needs and balance, and the availability
of funds.
Inquiries concerning this program announcement are encouraged.  The
opportunity to clarify any issues or questions from potential
applicants is welcome.
Direct inquiries regarding treatment aspects of proposed research to:
Joanne Fertig, Ph.D.
Division of Clinical and Prevention Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402 MSC 7003
Bethesda, MD  20892-7003
Telephone:  (301) 443-0796
FAX:  (301) 443-8744
Email:  jfertig@willco.niaaa.nih.gov
Direct inquiries regarding the neuroscience and behavioral aspects of
proposed research to:
Walter Hunt, Ph.D.
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402 MSC 7003
Bethesda, MD  20892-7003
Telephone:  (301) 443-4223
FAX:  (301) 594-0673
Email:  whunt@willco.niaaa.nih.gov
Direct inquiries regarding fiscal matters to:
Joseph Weeda
Office of Planning and Resource Management
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 504 MSC 7003
Bethesda, MD  20892-7003
Telephone:  (301) 443-4703
FAX:  (301) 443-3891
Email:  jweeda@willco.niaaa.nih.gov
This program is described in the Catalog of Federal Domestic
Assistance, No. 93.273.  Awards are made under the authorization of
the Public Health Service Act, Sections 301 and 464H, and
administered under the PHS policies and Federal Regulations at Title
42 CFR Part 52 and 45 CFR Part 74.  This program is not subject to
the intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review.
The PHS strongly encourages all grant recipients to provide a
smoke-free workplace and promote the non-use of all tobacco products.
In addition, Public Law 103-227, the Pro-Children Act of 1994,
prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education,
library, day care, health care or early childhood development
services are provided to children. This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.

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