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Adaptation of Brain Glutamate Plus Glutamine during Abstinence from Chronic Methamphetamine Use

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Abstract

Methamphetamine (METH) is a stimulant drug that is toxic primarily to dopaminergic and serotonergic neurons and may lead to inflammatory changes in the brain. Additionally, the glutamatergic system is altered following METH exposure. Therefore, concentrations of brain glutamate + glutamine (GLX) were assessed during abstinence from chronic METH abuse. Twenty-five subjects with a history of METH dependence (age 31.8 ± 7.4 years, 14 women and 11 men) and 28 control subjects without a history of drug abuse (age 32.6 ± 8.8 years, 14 women) were enrolled. Twelve of the METH subjects were followed and rescanned 5 months later. METH users had used the drug 5.9 ± 1.7 times per week, for 109 ± 69 months, and had been abstinent for 2.1 ± 3.0 months. GLX was measured in the basal ganglia and frontal gray and white matter, using proton magnetic resonance spectroscopy. While overall GLX concentrations at baseline were similar between METH and control subjects, METH users with less than or equal to 1 month of abstinence showed reduced frontal gray matter GLX (p = 0.01). Time of abstinence correlated positively with GLX in frontal gray (p < 0.0001) and white matter (p = 0.03). After 5 months, changes in frontal gray matter GLX showed a trend to correlate inversely with the duration of abstinence (p = 0.07). Subjects with craving symptoms had lower frontal gray matter GLX than those without craving (−8%, p = 0.05). These findings suggest dynamic abnormalities in brain GLX in recently abstinent METH users, with a depletion of the glutamatergic system in METH users within the first 2 months of abstinence and some normalization during prolonged abstinence. Since craving may contribute to relapse, medications that normalize GLX may minimize craving in METH users.

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Acknowledgments

This study was supported by the National Institute on Drug Abuse (NIDA, K-20 DA00280 and K-24 DA016170 for L.C. and K-02 DA16991 for T.E.) and the National Center for Research Resources (NCRR, a Clinical Research Center grant M01 000425). We also thank Dianne Osborn and Jorge Jovicich for assistance with magnetic resonance data acquisition, Nina Ames and Neha Trivedi for subject coordination, and Caroline Jiang for some of the statistical analyses. Both authors received research funding from the National Institutes of Health, and Dr. Ernst additionally received research funding from Siemens Medical Solutions; however, they did not have any other conflicts of interest relevant to this work.

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Authors and Affiliations

  1. Department of Medicine, John A. Burns School of Medicine, The University of Hawaii at Manoa, 1356 Lusitana Street, 7th floor, Honolulu, HI, 96813, Hawaii

    Thomas Ernst & Linda Chang

  2. The Queen’s Medical Center, Honolulu, HI, Hawaii

    Thomas Ernst & Linda Chang

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  1. Thomas Ernst
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  2. Linda Chang
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Correspondence to Thomas Ernst.

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Ernst, T., Chang, L. Adaptation of Brain Glutamate Plus Glutamine during Abstinence from Chronic Methamphetamine Use. J Neuroimmune Pharmacol 3, 165–172 (2008). https://doi.org/10.1007/s11481-008-9108-4

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  • DOI: https://doi.org/10.1007/s11481-008-9108-4

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