This application requests initial support for an Exploratory Center for Translational Research on the Clinical Neurobiology of Drug Addiction (P20). The proposed UCSD Center on Interoceptive Dysregulation in Addiction (CIDIA) addresses the global question: """"""""How does the brain regulate the urge to use?"""""""", with a focus initially on """"""""What is the role of interoceptive systems in general, and insular cortex in particular, in amphetamine addiction?"""""""" Interoception comprises sensing the physiological condition of the body, the conscious representation of this internal state within the context of ongoing activities, and the initiation of motivated action to regulate this state. Recent human and animal findings provide compelling evidence that interoceptive processing in the insula may mediate drug-related urges and preferences. Despite this evidence, it remains unclear how exactly the insula modulates these behaviors and what role interoceptive processing plays in different stages of addiction. To address these questions, we propose the following Specific Aims: (1) To determine the response characteristics of the interoceptive system using functional magnetic resonance imaging (fMRI) in adolescents and adults across stages of amphetamine use/addiction;(2) To delineate the causal role of interoceptive processing in mediating direct and conditioned rewarding or aversive effects in a rodent model using """"""""insula silencing"""""""" via reversible inactivation of neural activity with muscimol;and (3) To integrate results of animal and human studies and provide translational predictions by (a) developing animal models of interoceptive dysfunction, (b) using predictions from animal finding to modify human neuroimaging paradigms, and (c) modifying target structures of animal """"""""silencing"""""""" experiments based on human imaging studies. The goal for the Center is to impact the field of drug addiction in the following ways: (1) To develop and refine our understanding of the role of interoception for amphetamine dependence and, possibly, for addiction at large;(2) To develop translational paradigms to probe the sensitivity of the interoceptive system in animal models of drug addiction and humans in different stages of drug addiction;(3) To lay the groundwork for modulating the interoceptive system as a target for treatment;and (4) To discover risk factors or phenotypes for drug addiction involving interoceptive processing.

Public Health Relevance

Brain systems that sense the how you feel have recently been implicated in urge to use drugs. This center proposes to use animal experiments and human brain imaging studies to determine how these brain systems regulate the urge to use. Results from these experiments will provide (1) ways to monitor who is at high risk for developing drug addiction or who may relapse;(2) novel treatment targets for addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory Grants (P20)
Project #
5P20DA027843-04
Application #
8444669
Study Section
Special Emphasis Panel (ZDA1-MXS-M (09))
Program Officer
Grant, Steven J
Project Start
2010-03-15
Project End
2014-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
4
Fiscal Year
2013
Total Cost
$800,439
Indirect Cost
$235,195
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Squeglia, Lindsay M; Ball, Tali M; Jacobus, Joanna et al. (2016) Neural Predictors of Initiating Alcohol Use During Adolescence. Am J Psychiatry :appiajp201615121587
Paulus, Martin P; Huys, Quentin J M; Maia, Tiago V (2016) A Roadmap for the Development of Applied Computational Psychiatry. Biol Psychiatry Cogn Neurosci Neuroimaging 1:386-392
Mackey, Scott; Olafsson, Valur; Aupperle, Robin L et al. (2016) Greater preference consistency during the Willingness-to-Pay task is related to higher resting state connectivity between the ventromedial prefrontal cortex and the ventral striatum. Brain Imaging Behav 10:730-8
Berk, Lotte; Stewart, Jennifer L; May, April C et al. (2015) Under pressure: adolescent substance users show exaggerated neural processing of aversive interoceptive stimuli. Addiction 110:2025-36
Oosterwijk, Suzanne; Mackey, Scott; Wilson-Mendenhall, Christine et al. (2015) Concepts in context: Processing mental state concepts with internal or external focus involves different neural systems. Soc Neurosci 10:294-307
Gowin, Joshua L; Ball, Tali M; Wittmann, Marc et al. (2015) Individualized relapse prediction: Personality measures and striatal and insular activity during reward-processing robustly predict relapse. Drug Alcohol Depend 152:93-101
Stewart, Jennifer L; Juavinett, Ashley L; May, April C et al. (2015) Do you feel alright? Attenuated neural processing of aversive interoceptive stimuli in current stimulant users. Psychophysiology 52:249-62
Paulus, Martin P; Stewart, Jennifer L (2014) Interoception and drug addiction. Neuropharmacology 76 Pt B:342-50
Gowin, Joshua L; Harle, Katia M; Stewart, Jennifer L et al. (2014) Attenuated insular processing during risk predicts relapse in early abstinent methamphetamine-dependent individuals. Neuropsychopharmacology 39:1379-87
Stewart, Jennifer L; May, April C; Poppa, Tasha et al. (2014) You are the danger: attenuated insula response in methamphetamine users during aversive interoceptive decision-making. Drug Alcohol Depend 142:110-9

Showing the most recent 10 out of 26 publications