Relapse to drug abuse is the single greatest challenge in addiction treatment. Relapse can occur even after prolonged abstinence and is often preceded by robust drug craving precipitated by exposure to drug-paired stimuli and environments. Aerobic exercise is a novel and promising behavioral treatment for drug addiction and relapse. However, the precise mechanism of its therapeutic effects is unknown. The long-term goal of this project is to characterize the striatal network dynamics that mediate the effects of exercise on addiction and relapse. The current aims of this proposal are to examine the impact of chronic wheel running on rapid subsecond dopamine release dynamics and dopamine terminal function as well as on the longitudinal development of phasic dopamine signals that promote cocaine-seeking behavior and on the recruitment of cell- type specific neural processing of cocaine seeking and cocaine-paired cues. It is hypothesized that chronic wheel running will (1) attenuate cocaine-evoked subsecond dopamine release in the striatum, (2) decrease striatal phasic dopaminergic signals accompanying cocaine-paired cues and cocaine seeking, and (3) attenuate D1-MSN and potentiate D2-MSN encoding of cocaine-paired cues and cocaine seeking. These experiments will employ a sophisticated mouse model of cocaine relapse, state-of-the-art in vivo fast-scan cyclic voltammetry recordings, in vivo multiple single-unit electrophysiological recordings, and chemogenetic and optogenetic technologies to examine these questions in behaving animals. The proposed experiments aim to increase our understanding of the neurobiological substrates that mediate drug craving and relapse and identify the neurochemical and neurophysiological mechanisms of the beneficial effects of exercise.

Public Health Relevance

Drug abuse is a major public health concern, but currently, there are few effective treatments for managing drug craving and preventing relapse to drug use. Aerobic exercise is a promising treatment, but its precise mechanism of action is unknown. This project will help define the neurochemical and neurophysiological mechanisms that critically mediate the therapeutic effect of exercise on drug addiction and relapse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Career Transition Award (K99)
Project #
1K99DA047419-01A1
Application #
9820111
Study Section
Special Emphasis Panel (ZDA1)
Program Officer
Sorensen, Roger
Project Start
2019-08-01
Project End
2021-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201