Previous studies of cocaine dependence have sought to identify predictors of a positive treatment response, and have focused on personality traits, cognitive ability, and co-morbidity. In the first cycle of this award, our group investigated the rle of neurochemistry in success and failure to respond to a well-established behavioral treatment for cocaine dependence. Using Positron Emission Tomography (PET) and the radiotracer [11C]raclopride, we measured both D2/3 receptor binding potential (BPND) and stimulant-induced [11C]raclopride displacement (?BPND) in treatment-seeking cocaine dependent subjects. The scans were performed prior to subjects receiving a behavioral treatment that uses positive reinforcement (voucher incentives) for 24 weeks. The results showed that both PET outcome measures were increased in the subjects who responded to treatment compared to those who relapsed. In addition, both BPND and ?BPND did not differ between the treatment responders and a group of matched healthy controls. Thus, these results suggest that low dopamine transmission is associated with a greater likelihood of a poor treatment response, and that treatment responders may have intact dopamine signaling. The goal of this competing renewal is to use imaging to further expand our understanding of the deficit of dopamine transmission seen in treatment non-responders. The first goal will be to replicate the finding seen in cycle one with [11C]raclopride and a stimulant challenge. In order to better characterize the deficit in dopamine signaling, PET scans will be also performed with the radiotracer [18F]DOPA, which provides a measure of pre-synaptic dopamine synthesis and storage. In addition, fMRI scans will be performed to probe the reward system. Combined, these imaging studies will provide an understanding of the differences in striatal dopamine transmission and activation of reward pathways that differentiate cocaine dependent subjects who respond to treatment compared to those who relapse, and can be used to direct future treatment development.

Public Health Relevance

Since some participants with cocaine dependence respond to treatment, while other do not, the goal of this study is to better understand the signaling in the brain that is associated with this difference. Using functional neuroimaging, our goal is to study the neurochemistry, specifically dopamine transmission, in cocaine dependent subjects who do not respond to a well- established behavioral treatment. This data can then be used in future studies that develop treatments for this disorder.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01DA020855-06
Application #
8727499
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Grant, Steven J
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10032
Luo, Sean X; Martinez, Diana; Carpenter, Kenneth M et al. (2014) Multimodal predictive modeling of individual treatment outcome in cocaine dependence with combined neuroimaging and behavioral predictors. Drug Alcohol Depend 143:29-35
Tau, Gregory Z; Marsh, Rachel; Wang, Zhishun et al. (2014) Neural correlates of reward-based spatial learning in persons with cocaine dependence. Neuropsychopharmacology 39:545-55
Carpenter, Kenneth M; Martinez, Diana; Vadhan, Nehal P et al. (2012) Measures of attentional bias and relational responding are associated with behavioral treatment outcome for cocaine dependence. Am J Drug Alcohol Abuse 38:146-54
Martinez, Diana; Carpenter, Kenneth M; Liu, Fei et al. (2011) Imaging dopamine transmission in cocaine dependence: link between neurochemistry and response to treatment. Am J Psychiatry 168:634-41
Martinez, Diana; Orlowska, Daria; Narendran, Rajesh et al. (2010) Dopamine type 2/3 receptor availability in the striatum and social status in human volunteers. Biol Psychiatry 67:275-8