FUNCTIONAL GENOMICS OF COCAINE SELF ADMINISTRATION

Project: Research project

Project Details

Description

DESCRIPTION (Applicant's Abstract): Cocaine and crack addiction remains a
significant medical and social problem. While the dopamine transporter is
thought to be the primary site of action for the acute reinforcing effects of
cocaine, the post-synaptic consequences of cocaine use and the neurobiological
mechanisms that subserve the addictive process remain to be confirmed. The
identification of the genetic components underlying cocaine addiction is a
critical step in identifying potential targets for therapeutic intervention.
The central hypothesis of this application is that chronic drug abuse produces
a metastable epigenetic imprint that may contribute to clinical issues such as
tolerance, physical dependence, and withdrawal. This application proposes to
use multiplex DNA hybridization arrays to examine the interface of functional
genomics and behavior. - In Specific Aim # 1, DNA hybridization arrays will be
used to profile the CNS epigenetic imprint induced by cocaine
self-administration in rats. This will be accomplished using commercially
available arrays as well as custom arrays, imprinted at this institution and
designed to test specific hypotheses regarding cocaine abuse. These will then
be followed by studies in Specific Aim #2 that examine a new binge abstinence
model of cocaine administration. This model recapitulates several key features
of human cocaine abuse (specifically, the progressive loss of behavioral
control). Finally, studies at the end of the funding period (Specific Aim #3)
will establish the time course for gene expression changes following cessation
of cocaine self-administration. These last experiments will provide very
important insights into the stable changes in gene expression that survive
long-term cessation of the drug, while simultaneously identifying new genes
whose expression is altered during the withdrawal period. In addition to the
specific proposed experiments, efforts will be coordinated with Emory
University, during the funding period, to establish a central repository for
array data for general access by the NIDA research community
(www.arraydata.org) as well as a tissue/RNA bank. The results of the studies
described within the present application should provide a wealth of information
concerning functional genomic contributions to the cocaine addiction process.
StatusFinished
Effective start/end date9/30/005/31/01

Funding

  • National Institute on Drug Abuse: $355,457.00

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