Drug addiction can be characterized by the impaired abilities to choose the course of action that is likely to lead to the best long-term consequences for the affected individual and society. In particular, two different forms of impulsivity might both contribute to the initiation of addictive behaviors and become exacerbated by them. First, compared to healthy controls, drug addicts tend to show stronger preference for an immediate reward over a more delayed but larger reward. This is referred to as choice impulsivity. Second, drug abusers tend to initiate actions prematurely before the sufficient evidence for such actions is accumulated. This is referred to as response impulsivity. A main goal of Project 3 is to invesfigate how these two types of impulsivity might be mediated by the striatum in primates, and to test whether cocaine-induced changes in striatal functions might account for changes in the impulsive choices and responses. To investigate choice impulsivity, animals will be trained to perform an inter-temporal choice in which they will choose between two different rewards that differ in their magnitude and immediacy. Their choice impulsivity will be estimated from the steepness of a discount function that describes how the subjective value of reward decreases with the reward delay. Response impulsivity will be measured with a stop-signal task in which the animal receives an instrucfion to produce an eye movement towards a peripheral target in every trial but is also required to cancel such movement when a second """"""""stop"""""""" signal is presented. The time necessary to cancel the unwanted movement will be estimated to quantify response impulsivity. We will then characterize and compare the activity of individual neurons in the caudate nucleus and ventral striatum while the animals perform each of these two tasks before and after cocaine exposure. Specifically, we will test whether the striatal acfivity related to the reward magnitude and delay will be differenfially affected by cocaine exposure. We will also test whether the striatal activity related to the preparation and cancellation of visually guided eye movements are modified by cocaine. The results from these experiments will elucidate the role of striatum in drug addiction.

Public Health Relevance

Abnormal preference for an immediate but less desirable option and impaired abilities to suppress unwanted actions are main characteristics of addicfive behaviors. The proposed studies will investigate the role of the primate striatum in mediating such impulsive behaviors and how cocaine-induced changes in impulsive behaviors can be accounted for by the altered striatal functions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory Grants (P20)
Project #
1P20DA027844-01
Application #
7797227
Study Section
Special Emphasis Panel (ZDA1-MXS-M (09))
Project Start
2010-08-01
Project End
2014-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
1
Fiscal Year
2010
Total Cost
$167,469
Indirect Cost
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Worhunsky, Patrick D; Potenza, Marc N; Rogers, Robert D (2017) Alterations in functional brain networks associated with loss-chasing in gambling disorder and cocaine-use disorder. Drug Alcohol Depend 178:363-371
Yip, Sarah W; Morie, Kristen P; Xu, Jiansong et al. (2017) Shared microstructural features of behavioral and substance addictions revealed in areas of crossing fibers. Biol Psychiatry Cogn Neurosci Neuroimaging 2:188-195
Ren, Yudan; Fang, Jun; Lv, Jinglei et al. (2017) Assessing the effects of cocaine dependence and pathological gambling using group-wise sparse representation of natural stimulus FMRI data. Brain Imaging Behav 11:1179-1191
Worhunsky, Patrick D; Matuskey, David; Gallezot, Jean-Dominique et al. (2017) Regional and source-based patterns of [11C]-(+)-PHNO binding potential reveal concurrent alterations in dopamine D2 and D3 receptor availability in cocaine-use disorder. Neuroimage 148:343-351
Xu, Jiansong; Potenza, Marc N; Calhoun, Vince D et al. (2016) Large-scale functional network overlap is a general property of brain functional organization: Reconciling inconsistent fMRI findings from general-linear-model-based analyses. Neurosci Biobehav Rev 71:83-100
Schulte, Erica M; Yokum, Sonja; Potenza, Marc N et al. (2016) Neural systems implicated in obesity as an addictive disorder: from biological to behavioral mechanisms. Prog Brain Res 223:329-46
Pitts, Elizabeth G; Taylor, Jane R; Gourley, Shannon L (2016) Prefrontal cortical BDNF: A regulatory key in cocaine- and food-reinforced behaviors. Neurobiol Dis 91:326-35
Balodis, Iris M; Kober, Hedy; Worhunsky, Patrick D et al. (2016) Neurofunctional Reward Processing Changes in Cocaine Dependence During Recovery. Neuropsychopharmacology 41:2112-21
Gogliettino, Alex R; Potenza, Marc N; Yip, Sarah W (2016) White matter development and tobacco smoking in young adults: A systematic review with recommendations for future research. Drug Alcohol Depend 162:26-33
Gourley, Shannon L; Zimmermann, Kelsey S; Allen, Amanda G et al. (2016) The Medial Orbitofrontal Cortex Regulates Sensitivity to Outcome Value. J Neurosci 36:4600-13

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