Cocaine addiction respresents a devastating human condition. The complexities of drug addictions have slowed the development of effective prevention and treatment strategies. Impulsivity is an important construct that has been linked to the vulnerability to addictive processes. Additionally, the exposure to addictive drugs has been associated with increased impulsivity. However, the relationhip between impulsivity and addiction appears complex and pooriy understood, partially because of the complexity of impulsivity. Impulsivity has been found to factor into two main domains (choice and response) that appear associated with different aspects of drug addiction. However, the neurobiological substrates of these forms of impulsivity in drug addiction are not well understood. We propose investigating in individuals with and without cocaine dependence the neural substrates of choice and response impulsivity using functional magnetic resonance imaging (fMRI), with specific paradigms assessing each domain. Additionally, we will collect fMRI data to assess cognitive control and reward processing in the same subjects. Subjects in this project will also participate in project 2 assessing striatal dopamine D2/D3 receptor function and in the Clinical and Educational Core in which a comprehensive battery of clinical and neurcognitive measures will be obtained. This information will include information on stimulant influences on choice and response impulsivity and (amongst the cocaine dependent subjects) cocaine self administration. By integrating information across studies, a more complete understanding of the brain function underiying impulsivity as it relates to cocaine addiction will be achieved. Such information has significant potential to inform investigations into more effective prevention and treatment strategies for cocaine addiction.

Public Health Relevance

Human drug addiction represents a significant public health problem. The proposed investigation into the neurobiological processes underiying impulsivity in cocaine dependence will help improve our understanding of this complex condition.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Exploratory Grants (P20)
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Special Emphasis Panel (ZDA1-MXS-M)
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Yale University
New Haven
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