Drug abuse and obesity, two of our nation's most serious health concerns, are forms of addiction that share similar behavioral and neurobiological mechanisms. The goal of the proposed interdisciplinary and translational research is to examine cocaine abuse and binge eating disorder (BED) that leads to obesity with innovative behavioral and neuroimaging methodology. It is hypothesized that impulsivity is a major factor in these two forms of addiction, and GABA, the major inhibitory neurotransmitter in the brain, is reduced in addicted individuals. The proposed Center for the Study of Impulsivity in Addiction (CSIA) will focus on impulsive behavior, the GABA system, and neuroimaging in addiction-prone and -resistant individuals. Two clinical projects, involving cocaine abusers and BED patients (and controls), a preclinical component using animal models of critical phases of drug abuse, and three cores (neuroimaging, neurocognitive, and administrative) will comprise the CSIA. The Center will implement a translational approach using innovative animal models that predict vulnerability and test a GABA-related treatment to inform human studies with knowledge of key variables controlling the addictive behaviors. Our expertise with magnetic resonance (MR) imaging and behavioral measurements will be preclinical and clinical strengths of the Center.
Specific aims i nclude: 1) To examine impulsive behavior as it predicts (preclinical) and correlates with (clinical) cocaine abuse and BED and as it relates to measures of sweet preference, as a proclivity for sweet tastes predicts drug abuse, covaries with impulsiveness, and may be a useful predictive and diagnostic tool. 2) To investigate the role of GABA levels and white matter abnormalities in regions of the brain that is associated with impulsivity and addictive behavior. 3) To study commonalities among addictive behaviors (cocaine abuse and binge eating) using behavioral, MR imaging, and neurobiological techniques (e.g., GABA selective treatment drugs) that may lead to strategies for intervention. 4) To use MR imaging, both diffusion tensor imaging (DTI) to observe white matter abnormalities, and spectroscopy (MRS) that reveal neurochemical status, particularly GABA, and how imaging results differ in addiction-prone vs. controls, and rats with different addiction-vulnerable phenotypes will be compared on similar impulsivity tests and imaging procedures. 5) To compare results on all measures in males and females, as increasing evidence indicates sex differences in addictive behavior. 6) To build upon existing collaborative relationships and scientific expertise among NIDA-funded investigators the proposed collaboration will offer bench-to bedside, translational efforts for the prediction, prevention, and treatment of drug abuse and BED leading to obesity.
The proposed center should improve our understanding of the neurobiology of inhibitory control, which will lead to new approaches for prevention and treatment for addictive disorders.
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