 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, December 1, 2001, 21(23):9414-9418
Loss of Dopamine Transporters in Methamphetamine Abusers Recovers with Protracted Abstinence
Nora D. Volkow1, 3, Linda Chang1, 3, Gene-Jack Wang1, Joanna S. Fowler2, Dinko Franceschi1, Mark Sedler3, Samuel J. Gatley1, Eric Miller4, Robert Hitzemann3, Yu-Shin Ding1, and Jean Logan1 1 Medical and 2 Chemistry Departments, Brookhaven National Laboratory, Upton, New York 11973, 3 Department of Psychiatry, State University of New York at Stony Brook, Stony Brook, New York 11794, and 4 Department of Psychiatry, Harbor-University of California, Los Angeles, Torrance, California 90502
Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [11C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (<6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, +19%; putamen, +16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.
Key words: methamphetamine; dopamine transporters; imaging; positron emission tomography; addiction; detoxification; neurotoxicity; dopamine terminal
Copyright © 2001 Society for Neuroscience 0270-6474/01/21239414-05$05.00/0
This article has been cited by other articles:
M. Schwendt, A. Rocha, R. E. See, A. M. Pacchioni, J. F. McGinty, and P. W. Kalivas
Extended Methamphetamine Self-Administration in Rats Results in a Selective Reduction of Dopamine Transporter Levels in the Prefrontal Cortex and Dorsal Striatum Not Accompanied by Marked Monoaminergic Depletion
J. Pharmacol. Exp. Ther., November 1, 2009; 331(2): 555 - 562.
[Abstract] [Full Text] [PDF]
I. Boileau, P. Rusjan, S. Houle, D. Wilkins, J. Tong, P. Selby, M. Guttman, J. A. Saint-Cyr, A. A. Wilson, and S. J. Kish
Increased Vesicular Monoamine Transporter Binding during Early Abstinence In Human Methamphetamine Users: Is VMAT2 a Stable Dopamine Neuron Biomarker?
J. Neurosci., September 24, 2008; 28(39): 9850 - 9856.
[Abstract] [Full Text] [PDF]
K. A. Josephs
Capgras Syndrome and Its Relationship to Neurodegenerative Disease
Arch Neurol, December 1, 2007; 64(12): 1762 - 1766.
[Abstract] [Full Text] [PDF]
T. Hatzipetros, J. G. Raudensky, J.-J. Soghomonian, and B. K. Yamamoto
Haloperidol Treatment after High-Dose Methamphetamine Administration Is Excitotoxic to GABA Cells in the Substantia Nigra Pars Reticulata
J. Neurosci., May 30, 2007; 27(22): 5895 - 5902.
[Abstract] [Full Text] [PDF]
A. L. Malizia
The role of emission tomography in pharmacokinetic and pharmacodynamic studies in clinical psychopharmacology
J Psychopharmacol, July 1, 2006; 20(4_suppl): 100 - 107.
[Abstract] [PDF]
W. Jeng, A. Ramkissoon, T. Parman, and P. G. Wells
Prostaglandin H synthase-catalyzed bioactivation of amphetamines to free radical intermediates that cause CNS regional DNA oxidation and nerve terminal degeneration
FASEB J, April 1, 2006; 20(6): 638 - 650.
[Abstract] [Full Text] [PDF]
Y. Sekine, Y. Ouchi, N. Takei, E. Yoshikawa, K. Nakamura, M. Futatsubashi, H. Okada, Y. Minabe, K. Suzuki, Y. Iwata, et al.
Brain Serotonin Transporter Density and Aggression in Abstinent Methamphetamine Abusers
Arch Gen Psychiatry, January 1, 2006; 63(1): 90 - 100.
[Abstract] [Full Text] [PDF]
T. L. Jernigan, A. C. Gamst, S. L. Archibald, C. Fennema-Notestine, M. R. Mindt, T. L. Marcotte, R. K. Heaton, R. J. Ellis, and I. Grant
Effects of Methamphetamine Dependence and HIV Infection on Cerebral Morphology
Am J Psychiatry, August 1, 2005; 162(8): 1461 - 1472.
[Abstract] [Full Text] [PDF]
M. Cherner, S. Letendre, R. K. Heaton, J. Durelle, J. Marquie-Beck, B. Gragg, I. Grant, and the HIV Neurobehavioral Research Center Group
Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine
Neurology, April 26, 2005; 64(8): 1343 - 1347.
[Abstract] [Full Text] [PDF]
T. E. Nordahl, R. Salo, Y. Natsuaki, G. P. Galloway, C. Waters, C. D. Moore, S. Kile, and M. H. Buonocore
Methamphetamine Users in Sustained Abstinence: A Proton Magnetic Resonance Spectroscopy Study
Arch Gen Psychiatry, April 1, 2005; 62(4): 444 - 452.
[Abstract] [Full Text] [PDF]
L. Chang, T. Ernst, O. Speck, and C. S. Grob
Additive Effects of HIV and Chronic Methamphetamine Use on Brain Metabolite Abnormalities
Am J Psychiatry, February 1, 2005; 162(2): 361 - 369.
[Abstract] [Full Text] [PDF]
S. Jayanthi, X. Deng, B. Ladenheim, M. T. McCoy, A. Cluster, N.-s. Cai, and J. L. Cadet
Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis
PNAS, January 18, 2005; 102(3): 868 - 873.
[Abstract] [Full Text] [PDF]
G.-J. Wang, N. D. Volkow, L. Chang, E. Miller, M. Sedler, R. Hitzemann, W. Zhu, J. Logan, Y. Ma, and J. S. Fowler
Partial Recovery of Brain Metabolism in Methamphetamine Abusers After Protracted Abstinence
Am J Psychiatry, February 1, 2004; 161(2): 242 - 248.
[Abstract] [Full Text] [PDF]
S. JAYANTHI, X. DENG, P.-A. H. NOAILLES, B. LADENHEIM, and J. L. CADET
Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades
FASEB J, February 1, 2004; 18(2): 238 - 251.
[Abstract] [Full Text] [PDF]
J. L. CADET, S. JAYANTHI, and X. DENG
Speed kills: cellular and molecular bases of methamphetamine-induced nerve terminal degeneration and neuronal apoptosis
FASEB J, October 1, 2003; 17(13): 1775 - 1788.
[Abstract] [Full Text] [PDF]
Y. Sekine, Y. Minabe, Y. Ouchi, N. Takei, M. Iyo, K. Nakamura, K. Suzuki, H. Tsukada, H. Okada, E. Yoshikawa, et al.
Association of Dopamine Transporter Loss in the Orbitofrontal and Dorsolateral Prefrontal Cortices With Methamphetamine-Related Psychiatric Symptoms
Am J Psychiatry, September 1, 2003; 160(9): 1699 - 1701.
[Abstract] [Full Text] [PDF]
T. E. Nordahl, R. Salo, and M. Leamon
Neuropsychological Effects of Chronic Methamphetamine Use on Neurotransmitters and Cognition: A Review
J Neuropsychiatry Clin Neurosci, August 1, 2003; 15(3): 317 - 325.
[Abstract] [Full Text] [PDF]
N. T. Bello, K. L. Sweigart, J. M. Lakoski, R. Norgren, and A. Hajnal
Restricted feeding with scheduled sucrose access results in an upregulation of the rat dopamine transporter
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2003; 284(5): R1260 - R1268.
[Abstract] [Full Text] [PDF]
J. Rosack
Studies Show How Speed Exacts Toll on Brain
Psychiatr News, January 18, 2002; 37(2): 17 - 17.
[Full Text]
|
|
|
|
 |
|