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Title: Recovery of dopamine transporters with methamphetamine detoxification is not linked to changes in dopamine release

Abstract

Methamphetamine’s widespread abuse and concerns that it may increase Parkinson’s disease led us to assess if the reported loss of dopamine transporters (DAT) in methamphetamine abusers (MA) reflected damage to dopamine neurons. Using PET with [11C]cocaine to measure DAT, and with [11C]raclopride to measure dopamine release (assessed as changes in specific binding of [11C]raclopride between placebo and methylphenidate), which was used as marker of dopamine neuronal function, we show that MA (n=16), tested during early detoxification, had lower DAT (20-30%) but overall normal DA release in striatum (except for a small decrease in left putamen), when compared to controls (n=15). In controls, DAT were positively correlated with DA release (higher DAT associated with larger DA increases), consistent with DAT serving as markers of DA terminals. In contrast, MA showed a trend for a negative correlation (p=0.07) (higher DAT associated with lower DA increases), consistent with reduced DA re-uptake following DAT downregulation. MA who remained abstinent nine-months later (n=9) showed significant increases in DAT (20%) but methylphenidate-induced dopamine increases did not change. In contrast, in controls, DAT did not change when retested 9 months later but methylphenidate-induced dopamine increases in ventral striatum were reduced (p=0.05). Baseline D2/D3 receptors in caudate weremore » lower in MA than in controls and did not change with detoxification, nor did they change in the controls upon retest. The loss of DAT in the MA, which was not associated with a concomitant reduction in dopamine release as would have been expected if DAT loss reflected DA terminal degeneration; as well as the recovery of DAT after protracted detoxification, which was not associated with increased dopamine release as would have been expected if DAT increases reflected terminal regeneration, indicate that the loss of DAT in these MA does not reflect degeneration of dopamine terminals.« less

Authors:
 [1];  [2];  [2];  [3];  [2];  [2];  [2]
  1. National inst. on Alcohol Abuse and Alcoholism, Bethesda, MD (United States); Brookhaven National Lab. (BNL), Upton, NY (United States)
  2. National inst. on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)
  3. Brookhaven National Lab. (BNL), Upton, NY (United States)
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
National Institute of Health, Bethesda, MD (United States)
OSTI Identifier:
1239786
Report Number(s):
BNL-111679-2015-JA
Journal ID: ISSN 1053-8119; R&D Project: MO-085
Grant/Contract Number:  
SC0012704
Resource Type:
Accepted Manuscript
Journal Name:
NeuroImage
Additional Journal Information:
Journal Volume: 121; Journal Issue: C; Journal ID: ISSN 1053-8119
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; addiction; neurotoxicity; dopamine terminal; Parkinson's disease

Citation Formats

Volkow, Nora D., Wang, Gene-Jack, Smith, Lisa, Fowler, Joanna S., Telang, Frank, Logan, Jean, and Tomasi, Dardo. Recovery of dopamine transporters with methamphetamine detoxification is not linked to changes in dopamine release. United States: N. p., 2015. Web. doi:10.1016/j.neuroimage.2015.07.035.
Volkow, Nora D., Wang, Gene-Jack, Smith, Lisa, Fowler, Joanna S., Telang, Frank, Logan, Jean, & Tomasi, Dardo. Recovery of dopamine transporters with methamphetamine detoxification is not linked to changes in dopamine release. United States. https://doi.org/10.1016/j.neuroimage.2015.07.035
Volkow, Nora D., Wang, Gene-Jack, Smith, Lisa, Fowler, Joanna S., Telang, Frank, Logan, Jean, and Tomasi, Dardo. Tue . "Recovery of dopamine transporters with methamphetamine detoxification is not linked to changes in dopamine release". United States. https://doi.org/10.1016/j.neuroimage.2015.07.035. https://www.osti.gov/servlets/purl/1239786.
@article{osti_1239786,
title = {Recovery of dopamine transporters with methamphetamine detoxification is not linked to changes in dopamine release},
author = {Volkow, Nora D. and Wang, Gene-Jack and Smith, Lisa and Fowler, Joanna S. and Telang, Frank and Logan, Jean and Tomasi, Dardo},
abstractNote = {Methamphetamine’s widespread abuse and concerns that it may increase Parkinson’s disease led us to assess if the reported loss of dopamine transporters (DAT) in methamphetamine abusers (MA) reflected damage to dopamine neurons. Using PET with [11C]cocaine to measure DAT, and with [11C]raclopride to measure dopamine release (assessed as changes in specific binding of [11C]raclopride between placebo and methylphenidate), which was used as marker of dopamine neuronal function, we show that MA (n=16), tested during early detoxification, had lower DAT (20-30%) but overall normal DA release in striatum (except for a small decrease in left putamen), when compared to controls (n=15). In controls, DAT were positively correlated with DA release (higher DAT associated with larger DA increases), consistent with DAT serving as markers of DA terminals. In contrast, MA showed a trend for a negative correlation (p=0.07) (higher DAT associated with lower DA increases), consistent with reduced DA re-uptake following DAT downregulation. MA who remained abstinent nine-months later (n=9) showed significant increases in DAT (20%) but methylphenidate-induced dopamine increases did not change. In contrast, in controls, DAT did not change when retested 9 months later but methylphenidate-induced dopamine increases in ventral striatum were reduced (p=0.05). Baseline D2/D3 receptors in caudate were lower in MA than in controls and did not change with detoxification, nor did they change in the controls upon retest. The loss of DAT in the MA, which was not associated with a concomitant reduction in dopamine release as would have been expected if DAT loss reflected DA terminal degeneration; as well as the recovery of DAT after protracted detoxification, which was not associated with increased dopamine release as would have been expected if DAT increases reflected terminal regeneration, indicate that the loss of DAT in these MA does not reflect degeneration of dopamine terminals.},
doi = {10.1016/j.neuroimage.2015.07.035},
journal = {NeuroImage},
number = C,
volume = 121,
place = {United States},
year = {Tue Jul 21 00:00:00 EDT 2015},
month = {Tue Jul 21 00:00:00 EDT 2015}
}

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