# Exercise in Methamphetamine Use Disorder: Dopamine Receptor Upregulation and Neural Function

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $661,715

## Abstract

PROJECT SUMMARY/ABSTRACT
 With no approved medications for methamphetamine (MA) use disorder, a major public health problem,
new treatment approaches are needed. Striatal dopamine D2-type receptor (DRD2/3) availability (binding
potential, BPND) is linked to indices of cognitive control, and MA users show deficits in both. Striatal DRD2/3
BPND release can predict outcomes of behavioral treatments for stimulant dependence. Thus, DRD2/3 signaling
is a logical therapeutic target, but dopamine agonists have not been successful treatments, perhaps due to
underlying pathology involving DRD2/3. We suggest that promoting dopaminergic neuroplasticity may
ameliorate neurobehavioral problems associated with MA use disorder. Our preliminary data indicate that
adding an exercise program can increase striatal DRD2/3 BPND in MA users receiving behavioral treatment. If
such an increase can improve neurocognitive function, it may be a useful therapeutic adjunct for stimulant use
disorders. We have shown that in healthy control subjects, striatal DRD2/3 BPND is linked with performance and
neural activity related to self-control and cognitive flexibility. To determine whether exercise can improve
function in these and other cognitive domains, we will randomize individuals with MA use disorder (males and
females, 18-45 years) in a residential behavioral treatment program to two groups: 1) Exercise-Group
participants will be in an 8-week, moderate-intensity exercise training program; 2) Control-Group participants
will be in parallel health-education sessions with equal time and supervision. We will assess DRD2/3 BPND with
PET, and neural activity in tests of inhibitory control and cognitive flexibility during fMRI. We have four specific
aims: 1) confirm that adding exercise to behavioral treatment produces striatal DRD2/3 upregulation in MA
users; 2) compare effects of the exercise and control conditions on performance and associated neural activity
during tests of inhibitory control and cognitive flexibility, and on performance in a cognitive battery; 3) test
whether effects on cognitive control and brain function are related to changes in DRD2/3 BPND; and 4) compare
the effects of the exercise and control conditions on simulated MA choice and actual MA use. We expect that:
1) BPND will increase more in the exercise condition than the control condition; 2) the exercise group will show
more improvement than the controls in task performance and activation within executive-control regions during
fMRI, and in performance on a cognitive test battery; 3) DRD2/3 BPND increases in exercise-group participants
will be positively associated with changes in task performance and neural activity; and 4) both virtual MA
choice, measured in the laboratory, and MA use, measured by self-report and urine tests at follow-up, will be
lower in participants in the exercise group and will be negatively related to DRD2/3 BPND at the end of the
intervention. The use of exercise training as a ...

## Key facts

- **NIH application ID:** 10153743
- **Project number:** 5R01DA045162-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Edythe Danick London
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $661,715
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153743

## Citation

> US National Institutes of Health, RePORTER application 10153743, Exercise in Methamphetamine Use Disorder: Dopamine Receptor Upregulation and Neural Function (5R01DA045162-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153743. Licensed CC0.

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