Cocaine addiction is a chronic, relapsing disorder for which there is little effective pharmacologic treatment. The preclinical literature suggests that the mesolimbic dopamine system is critically involved in the reinforcing effects of cocaine and in vulnerability to relapse. However, to date relatively little is known about the neurochernical changes in mesolimbic dopamine function in humans and their putative role in mediating cocaine seeking behavior. Recent developments in brain imaging provide the unique opportunity to study these changes and their role in cocaine addiction. During the proposed career development award, the candidate will learn to develop neuroreceptor imaging techniques with PET and to implement these techniques in the study of neurochemical imbalances in chronic cocaine abuse. In addition, the career development period will include training in human behavioral pharmacology, in order to relate brain imaging findings with cocaine taking behavior in humans. Columbia University provides a unique environment to achieve this purpose.
The specific aims i nclude the study of pre- and post-synaptic parameters of dopamine transmission in mesolimbic regions (ventral striatum and amygdala) in chronic cocaine users and matched healthy controls. Alterations of dopamine transmission will then be related to laboratory measures of cocaine self-administration following a low dose of cocaine (""""""""priming"""""""" dose). Based on preclinical literature, the hypotheses are that low mesolimbic D1 receptor density and high stimulant-induced dopamine release will be correlated with an increased likelihood of cocaine taking behavior in the laboratory. Thus, an unique aspect of this proposal is the combination of state-of-the-art PET technology and established laboratory methods for studying cocaine self-administration. The career development plan proposed in this application is designed both to address these scientific questions as well as to provide the principal investigator an unparalleled training in the neuroimaging and behavioral studies of substance abuse. Toward this aim, a comprehensive educational program including mentoring, didactics, and collaboration with experts in the field has been outlined in this application.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23DA000483-01
Application #
6166051
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Grant, Steven J
Project Start
2000-09-25
Project End
2005-08-31
Budget Start
2000-09-25
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$155,817
Indirect Cost
Name
Columbia University (N.Y.)
Department
Psychiatry
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Martinez, Diana; Slifstein, Mark; Gil, Roberto et al. (2009) Positron emission tomography imaging of the serotonin transporter and 5-HT(1A) receptor in alcohol dependence. Biol Psychiatry 65:175-80
Martinez, Diana; Slifstein, Mark; Narendran, Rajesh et al. (2009) Dopamine D1 receptors in cocaine dependence measured with PET and the choice to self-administer cocaine. Neuropsychopharmacology 34:1774-82
Lee, Dustin C; Myers, Carol S; Taylor, Richard C et al. (2007) Consistency of subjective responses to imagery-induced tobacco craving over multiple sessions. Addict Behav 32:2130-9
Martinez, Diana; Narendran, Rajesh; Foltin, Richard W et al. (2007) Amphetamine-induced dopamine release: markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine. Am J Psychiatry 164:622-9