One of the defining features of addictive behavior is its persistence despite potentially severe adverse outcomes. To further understand why addicts fail to learn from negative outcomes, we propose to explore the role of a newly identified brain region, the rostromedial tegmental nucleus (RMTg), which we and others have recently shown to encode negative reward prediction errors, and to be critically involved in a variety of aversive behaviors. We hypothesize that impairment of this structure leads to an addiction phenotype in which animals persistently seek outcomes despite aversive outcomes. We propose two aims, the first of which is designed to better understand the basic mechanisms by which the RMTg contributes to learning about negative outcomes.
Our second aim i s more translational, exploring the role of the RMTg in cocaine-seeking under punishment, as well as its contribution to individual variation in propensity to develop addictive behaviors.

Public Health Relevance

One hallmark of an addictive behavior is its persistence despite large negative outcomes, which can take a variety of forms, include physically aversive outcomes (withdrawal, toxicity) or social, cognitive, and financial losses. To better understand the pathology underlying these behaviors, we will explore the mechanisms underlying our recent findings that lesions of the rostromedial tegmental nucleus (RMTg) render animals strikingly deficient in learning from aversive outcomes. This will facilitate better treatments for behavioral disorders in which individuals seek drug rewards despite the large costs they incur.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DA032898-02
Application #
8543692
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Volman, Susan
Project Start
2012-09-15
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$177,000
Indirect Cost
$57,000
Name
Medical University of South Carolina
Department
Neurosciences
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Bentzley, Brandon S; Jhou, Thomas C; Aston-Jones, Gary (2014) Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat. Proc Natl Acad Sci U S A 111:11822-7
Jhou, Thomas C; Good, Cameron H; Rowley, Courtney S et al. (2013) Cocaine drives aversive conditioning via delayed activation of dopamine-responsive habenular and midbrain pathways. J Neurosci 33:7501-12