Full Text PA-95-008

INNOVATIVE METHODS FOR SCREENING DRUGS TO TREAT COCAINE AND OPIATE ABUSE

NIH GUIDE, Volume 23, Number 41, November 25, 1994

PA NUMBER:  PA-95-008

P.T.


Keywords: 


National Institute on Drug Abuse

PURPOSE

The purpose of this program announcement is to encourage research to
develop innovative preclinical methods and model systems (for
example, in rodents or non-human primates) for the identification of
potential treatment agents for the entire spectrum of cocaine and
opioid abuse, from pre-addiction through abstinence, relapse, and
recovery.  The methods may be based upon behavioral,
neurophysiologic, neurochemical, or other approaches as long as a
strong case is made that they will be relevant to human cocaine and
opioid abuse and their pharmacologic treatment.  These methods should
be novel or they should significantly expand other undeveloped or
unrecognized methods and models as tools for evaluating
pharmacotherapies for drug abuse disorders.

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,  Innovative Methods for Screening Drugs to Treat
Cocaine and Opiate Abuse, is primarily related to the priority area
of alcohol and other drugs.  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, for-profit and non-profit
organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State or 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 and small grants (R03).

MECHANISM OF SUPPORT

The mechanisms available for support of this program announcement are
the regular research project grant (R01), the small grant award
(R03), and the FIRST award (R29).  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

Several behavioral models of drug abuse have been useful in studying
important variables in the laboratory.  Perhaps the most widely
recognized of these is the self-administration model in which an
animal presses a lever to inject an abused drug intravenously.  This
methodology has been an invaluable research tool in many ways,
especially in the preclinical evaluation of the abuse potential of
compounds.  The drug discrimination model is a second method that has
proven useful.  In this method, an animal is trained, on the basis of
internal (interoceptive) cues, to make one response when a particular
drug is injected, and to make a different response when a different
drug (or placebo) is injected.  This procedure has proved valuable in
assessing the subjective effects (e.g., the "high") of cocaine or
opioids, as well as the likelihood that an unknown compound produces
a similar interoceptive cue.

The self-administration and discrimination models in rodents and non-
human primates do not cover all aspects of human drug abuse and
addiction including drug seeking, initiation, maintenance, dose
escalation, extinction, relapse, remission, and recovery.  Animal
models to study the multiple phases of cocaine or opioid abuse have
not been well developed or validated.  This has hampered the
identification and development of new medications that may be useful
in treating abuse of these substances.  The development of such new
animal models promises to represent an important advance regarding
identification and development of a wider range of medications that
treat cocaine and opioid abuse.

At the present time, no validated models exist to represent the human
recovery phase following treatment for substance abuse in which the
subject strives not to return to previous behaviors, namely drug
seeking and drug taking.  This lack of suitable animal models
restricts the study of variables which contribute to relapse to drug
seeking behavior and drug taking.

Areas of research interest include those that are innovative, that
develop new methods of drug discovery for treatment of cocaine and
opioid abuse and that will advance the development of new medications
for treatment of abuse of these substances.  In general, these may
include, but are not limited to:

o  An innovative behavioral model for craving and/or drug seeking
behavior.

o  Techniques to study behavior after treatment for drug abuse as
experimental models of recovery and/or relapse.

o  Neurophysiologic and/or neurochemical techniques that utilize the
underlying mechanisms of cocaine and/or opioid abuse as means to
identify new potential pharmacotherapies.

These areas of research are not intended to be all-inclusive.
However, experimental models to develop therapeutic interventions for
cocaine and opioid abuse are extremely limited.  Within the area of
opioid abuse despite the availability of effective maintenance
medications, relapse is still a major issue.  Thus, a major research
effort is required to design innovative approaches to expand the
current methods and models to those that have not been explored.
Well-known models of drug abuse to study cocaine and opioid abuse are
of interest only insofar as their application constitutes an
innovative approach.  It is anticipated that no single method will be
definitive.  It is further anticipated that both behavioral and non-
behavioral techniques will be identified and developed.

The PHS Policy on Humane Care and Use of Laboratory Animals by Award
Institutions requires that applicant organizations establish and
maintain appropriate policies and procedures to ensure the humane
care and use of live vertebrates involved in research, research
training, and biological testing activities supported by the PHS.
All institutions are required to comply, as applicable, with the
Animal Welfare Act as amended (7 USC 2131 et sec.).  These documents
are available from the Office for Protection from Research Risks
(OPRR), National Institutes of Health, Bethesda, MD 20892.

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 Grants 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.

FIRST (R29) applications must include at least three sealed letters
of reference attached to the face page of the original application.
FIRST 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 of the PHS
398 form must be sent or delivered to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established PHS
referral guidelines.  Applications will be reviewed for scientific
and technical merit by a study section of the Division of Research
Grants, NIH (or by the review group of the relevant Institute, Center
or Division) in accordance with standard NIH peer review procedures.
Following scientific-technical review, the applications will receive
a second-level review by an appropriate national advisory council.

As part of the initial merit review, a process (triage) will be used
by the initial review group to determine whether an application is
competitive or non-competitive based on the scientific merit relative
to other applications received in response to the program
announcement.  Applications judged to be non-competitive will be
withdrawn from further consideration and the Principal Investigator
and the official signing for the applicant organization will be
notified.

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;

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:  quality of the proposed
project as determined by peer review; availability of funds; program
priority, needs and balance.

For applications assigned to the NIDA, preference will be given for
innovative methods to identify medications for treating cocaine and
opioid abuse.

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Heinz Sorer, Ph.D.
Medications Development Division
National Institute on Drug Abuse
5600 Fishers Lane, Room 11A-55
Rockville, MD  20857
Telephone:  (301) 443-6270
Email:  hsorer@aoada.ssw.dhhs.gov

Direct inquires regarding fiscal issues 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
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 intergovernmental
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.

The Public Health Service strongly encourages all grant recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.

.

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