Full Text PA-95-038

NEUROSCIENCE RESEARCH OF NICOTINE AND NICOTINE ABUSE

NIH GUIDE, Volume 24, Number 10, March 17, 1995

PA NUMBER:  PA-95-038

P.T. 34

Keywords: 
  Addiction 
  Smoking Behavior 
  Neuroscience 
  Neurophysiology 


National Institute on Drug Abuse

PURPOSE

The purpose of this program announcement is to encourage research to
examine the many aspects of nicotine abuse/addiction in in vitro or
in vivo systems, in animals, and in man.  The research may be based
upon behavioral, neurophysiologic, neurochemical, or other methods
that will seek to explain nicotine use.  The overall goal is to
further our understanding of the brain mechanisms that underlie
addictive processes, with an eventual target of developing specific
treatments for the abuse/addiction of nicotine in man.

HEALTHY PEOPLE 2000

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, Neuroscience Research of Nicotine and Nicotine Abuse,
is related to the priority area of tobacco.  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 202-783-3238).

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

The mechanism available for support of this program announcement is
the regular research project grant (R01).  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.

RESEARCH OBJECTIVES

Background

Throughout history, man has maintained the ubiquitous habit of
smoking, ingesting, or otherwise using tobacco products.  The most
common usage is inhalation of the smoke, with approximately 27
percent of the United States population lighting up cigarettes,
cigars, and pipes on a regular basis.  (1) Nicotine, the major
pharmacologic agent in tobacco, is widely accepted to be the primary
cause of this habit (2,3).

In the 1964 report of the Advisory Committee of the U.S. Surgeon
General on Smoking and Health, (3) the WHO Expert Committee criteria
were used as the basis for viewing tobacco as a "habit" rather than
an addiction.  The primary reasons for the decision to define
smoking, even heavy or compulsive smoking, as a habit was because of
the absence of clear-cut nicotine-induced signs of physical
dependence (withdrawal) in animal models, and of the belief that
symptoms observed when smokers stopped using tobacco were "secondary
to the deprivation of a desired object" rather than a specific
nicotine-induced withdrawal effect, and of the variable duration of
these cessation symptoms. Furthermore, there was the belief that the
obvious tolerance that smokers showed for tobacco was of "low grade,"
and that a variety of interventions that appeared to help the
motivated smoker in quitting this "habit."

In this historic document, it was implied many times (but never
actually stated) that the primary reason that people smoked tobacco
was to obtain nicotine.

Subsequent reports from the Surgeon General and from other
prestigious national and international forums (including the Royal
College of Physicians, (4) the American Psychiatric Association and
the World Health Organization have left little doubt as to the
addictive nature of nicotine.  These were summarized in the 1988
Surgeon General's Report which incorporated more than 2500 published
papers and the contributions of more than 50 scientists, and
presented three major conclusions:

1.  Cigarettes and other forms of tobacco are addictive,

2.  Nicotine is the drug in tobacco that causes addiction, and

3.  The pharmacological and behavioral processes that determine
tobacco addiction are similar to those that determine addiction to
drugs such as heroin and cocaine.

Because of the widespread use of cigarettes and other
nicotine-containing products and the recent suggestion that nicotine
may be "as addictive as cocaine", the National Institute on Drug
Abuse (NIDA) is seeking additional research into the many different
effects of nicotine.

Areas of Research

Areas of research interest in this program announcement range from
the in vitro biochemical and neurochemical determinations of the
effects of nicotine in model systems, to in vivo studies
investigating the behavioral or physiologic effects of nicotine in
animals and in man.

In general, these may include:

o  An examination of the cholinergic mechanisms involved, both
peripherally and centrally, in the effects of nicotine.

o  Further investigations of the subtypes of nicotinic cholinergic
receptors (alpha, beta, delta and gamma), and their correlation with
function.

o  Neurobiologic and/or neurochemical techniques that utilize the
underlying mechanisms of nicotine to understand the use/abuse of this
substance.

o  Studies of individual sensitivities of animal or human systems
toward the behavioral or physiologic effects of nicotine.

o  The development of new animal models of smoking that correlate
with the human pattern of nicotine self-administration.

o  A comparison of the neuroanatomical sites and the neurochemical
substrates in the addictive behavior of nicotine.

o  Effects of nicotine on cognitive performance, perception,
vigilance, memory and motor skills.

o  Neurotoxicologic effects of nicotine in animals and/or man.

o  Effects of prenatal nicotine on development and social behaviors
in the offspring.

o  Human studies on the prevalence of nicotine addiction in society
and its role in fostering attitudes towards other drugs of abuse.

o  Autoradiographic or computer imaging studies of tobacco
smoking/nicotine administration.

o  A comparison of behaviors (craving/withdrawal/relapse) of nicotine
and other abused drugs.

These areas of research are not intended to be all-inclusive, but are
designed to give the applicant some direction for the types of
research that NIDA is interested in exploring in its search to
understand the basic mechanism(s) of nicotine abuse, as well as other
abused drugs.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS

It is the policy of the NIH that women and 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 new policy results from the NIH
Revitalization Act of 1993 (Section 492B of Public Law 103-43) and
supersedes and strengthens the previous policies (concerning the
Inclusion of Women in Study Populations, and Concerning the Inclusion
of Minorities in Study Populations) which have been in effect since
1990.  The new policy contains some new provisions that are
substantially different from the 1990 policies.

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 reprinted
in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume
23, Number 11.

Investigators may obtain copies from these sources or from the
program staff or contact person listed below. Program staff also
provide additional relevant information concerning the policy.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS
398 (rev. 9/91) 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 Office of Grant Information, Division of
Research Grants, National Institutes of Health, Westwood Building,
Room 449, Bethesda, MD 20892, telephone 301/435-0714.  The title and
number of the program announcement must be typed in Item 2a of face
page of the application.

Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the GCRC as a resource for conducting
the proposed research.  If so, a letter of agreement from either the
GCRC program director or principal investigator could be included
with the application.

The completed original application and five legible copies of the
application must be sent or delivered to:

Division of Research Grants
National Institutes of Health
6701 Rockledge Drive, Room 1040 - MSC 7710
Bethesda, MD  20892-7710

If overnight delivery is used, the zip code is 20817.

REVIEW CONSIDERATIONS

Applications that are complete and responsive to the program
announcement 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 applications under
review, will be discussed, assigned a priority score, and receive a
second level review by the appropriate advisory council or board.

Review Criteria:

o  scientific, technical, or medical significance and originality of
proposed research;

o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;

o  qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of proposed research;

o  availability of the resources necessary to perform the research;

o  appropriateness of the proposed budget and duration in relation to
the proposed research; and

o  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.

The initial review group will also examine the provisions for the
protection of human and animals subjects, and the safety of the
research environment.

AWARD CRITERIA

Applications will compete for available funds with all other approved
applications assigned to the Institute.  The following will be
considered in making funding decisions:

o  quality of the proposed project as determined by peer review,

o  availability of funds,

o  programmatic priorities, i.e.,

o  relevance to program goals and objectives as described in the
Areas of Research Interest in the program announcement.

INQUIRIES

Inquiries are encouraged.  The opportunity to clarify any issues or
questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

David N. Johnson, Ph.D.
Division of Basic Research
National Institute on Drug Abuse
5600 Fishers Lane, Room 10A-19
Rockville, MD  20857
Telephone:  (301) 443-6975
FAX:  (301) 594-6043
Email:  dj42n@nih.gov

Direct inquiries regarding fiscal matters to:

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
5600 Fishers Lane, Room 8A-54
Rockville, MD  20857
Telephone:  (301) 443-6710
FAX:  (301) 594-6847
Email:  gfleming@aoada.ssw.dhhs.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.279.  Awards are made under authorization of
Section 301 of the Public Health Service Act (42 USC 241) and
administered under PHS policies and Federal Regulations at Title 42
CFR 52 "Grants for Research Projects,"  Title 45 CFR Part 74 & 92,
"Administration of Grants" and 45 CFR Part 46, "Protection of Human
Subjects."  This program is not subject to the inter- governmental
review requirements of Executive Order 12372 or Health Systems Agency
review.

Sections of the Code of Federal Regulations are available in booklet
form from the U.S. Government Printing Office.  Grants must be
administered in accordance with the PHS Grants Policy Statement,
(rev. 4/94), which may be available from your office of sponsored
research.

The PHS strongly encourages all grant and contract 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 routing 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.

Bibiolography

1.  U.S. Dept. of Health and Human Services. National Household
Survey on Drug Abuse: Main Findings 1990. DHHS Publication # (ADM)
91-1788. Washington, D.C. United States Government Printing Office,
1991.

2.  Nicotine Psychopharmacology (eds: S. Wonnacott, M.A.H. Russell,
I.P. Stolerman) Oxford Science Publications, p. 25, 1990.

3.  Reducing the Health Consequences of Smoking: Nicotine Addiction.
A Report of the Surgeon General. Rockville, MD. DHHS Publication #
(CDC) 88-8406. Washington, DC United States Government Printing
Office, 1988.

4.  Henningfield, JE, C Cohen and JD Slade. Is nicotine more
addictive than cocaine? Br. J. Addiction 86: 565-569, 1991.

.

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