Despite intensive research efforts, cocaine dependence (CD) remains a prevalent and costly disorder whose precise etiology remains poorly understood and thus poorly prevented and treated. Impulsivity has been increasingly recognized as an important factor that may predispose individuals to addiction as well as be modified by substance use to promote further engagement. Impulsivity constitutes a complex, multi-faceted construct that has been shown to involve separate domains of choice and response impulsivity. The striatum has been implicated in translational studies of addiction, with important contributions from both ventral and dorsal components to specific aspects of addiction. Striatal function has also been preliminarily linked to aspects of impulsivity. However, the manners in which aspects of impulsivity and regions of striatal function relate to one another and CD are poorly understood in this exploratory center, we seek to investigate these relationships in a series of tightly integrated, cohesive translational investigations. Specifically, CD and matched control subjects will participate in fMRI investigations using tasks of choice and response impulsivity to probe the underlying neural correlates as related to CD. These subjects will also be imaged with a novel, highly selective D2/D3 dopamine receptor agonist radiotracer, [11C] PHNO to investigate striatal dopamine function. Through a clinical core, the same subjects will be evaluated on a broad range of clinical, neurocognitive, and laboratory measures including challenges to assess stimulant effects on choice and response impulsivity and cocaine self administration in CD subjects. As such, the fMRI and PET projects will investigate the relationships between the neural measures and the clinical ones. Two additional projects will utilize the same choice and response impulsivity tasks and [11C] PHNO PET assessments in non-human primates and rats. These projects investigate cocaine influence on choice and response impulsivity and gather information on electrophysiological neuronal function and viral-mediated gene expression effects that are not possible in CD subjects. Together, data from these highly integrated, translational studies should advance our understanding of CD and help target the development of more effective prevention and treatment strategies.
Cocaine dependence is a significant public health problem. An improved understanding of the underlying neurobiology that might best be achieved through integrated translational research has significant potential to lead to breakthroughs that could prevent or effectively treat this devastating disorder.
|Balodis, Iris M; Potenza, Marc N (2015) Anticipatory reward processing in addicted populations: a focus on the monetary incentive delay task. Biol Psychiatry 77:434-44|
|Xian, Hong; Giddens, Justine L; Scherrer, Jeffrey F et al. (2014) Environmental factors selectively impact co-occurrence of problem/pathological gambling with specific drug-use disorders in male twins. Addiction 109:635-44|
|Hamilton, Kristen R; Sinha, Rajita; Potenza, Marc N (2014) Self-reported impulsivity, but not behavioral approach or inhibition, mediates the relationship between stress and self-control. Addict Behav 39:1557-64|
|Yarosh, Haley L; Hyatt, Christopher J; Meda, Shashwath A et al. (2014) Relationships between reward sensitivity, risk-taking and family history of alcoholism during an interactive competitive fMRI task. PLoS One 9:e88188|
|Xu, Jiansong; Calhoun, Vince D; Pearlson, Godfrey D et al. (2014) Opposite modulation of brain functional networks implicated at low vs. high demand of attention and working memory. PLoS One 9:e87078|
|Farr, Olivia M; Zhang, Sheng; Hu, Sien et al. (2014) The effects of methylphenidate on resting-state striatal, thalamic and global functional connectivity in healthy adults. Int J Neuropsychopharmacol 17:1177-91|
|Matuskey, David; Gallezot, Jean-Dominique; Pittman, Brian et al. (2014) Dopamine D? receptor alterations in cocaine-dependent humans imaged with [¹¹C](+)PHNO. Drug Alcohol Depend 139:100-5|
|Hamilton, Kristen R; Potenza, Marc N; Grunberg, Neil E (2014) Lewis rats have greater response impulsivity than Fischer rats. Addict Behav 39:1565-72|
|Zhang, Sheng; Li, Chiang-Shan R (2014) Functional clustering of the human inferior parietal lobule by whole-brain connectivity mapping of resting-state functional magnetic resonance imaging signals. Brain Connect 4:53-69|
|Rahman, Ardeshir S; Xu, Jiansong; Potenza, Marc N (2014) Hippocampal and amygdalar volumetric differences in pathological gambling: a preliminary study of the associations with the behavioral inhibition system. Neuropsychopharmacology 39:738-45|
Showing the most recent 10 out of 59 publications