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Withdrawal from long-term methamphetamine self-administration 'normalizes' neurometabolites in rhesus monkeys: a (1) H MR spectroscopy study.

ABSTRACT: (1) H magnetic resonance spectroscopy has demonstrated alterations in several neurometabolites in methamphetamine (METH)-dependent individuals in brain regions implicated in addiction. Yet, it is unclear whether these neurochemicals return to homeostatic levels after an individual abstains from drug use, a difficult question to address due to high recidivism and poor study retention in human subjects. We thus utilized a non-human primate model of addiction to explore the effects of long-term drug exposure and withdrawal on brain neurochemistry. Ten rhesus macaque monkeys on an active METH self-administration protocol (average use 4.6?±?0.8 years, average daily intake between 0.4 and 1.2?mg/kg) and 10 age- and sex-matched drug-naive controls (CONT) served as subjects. Concentrations of several neurochemicals were evaluated at several timepoints following withdrawal from drug availability (10 monkeys at 1 week and 1 and 3 months, and 6 monkeys at 6 and 12 months; CONT examined at one timepoint). At 1 week following METH withdrawal, we found increases in myo-inositol in anterior cingulate cortex in the METH group relative to CONT. These alterations showed a linear pattern of decreased levels ('normalization') by 1 year of abstinence. We also found decreases in glutamine and Glx (composed mainly of glutamate and glutamine) in the caudate-putamen of the same animals at early withdrawal that showed a similar linear pattern of increasing concentration by 1 year. These results demonstrate that despite protracted, long-term use, neurochemical changes seen following long-term drug administration do not persist following prolonged abstinence, suggesting therapeutic effects of long-term withdrawal from drug use.

SUBMITTER: Yang S

PROVIDER: S-EPMC3875627 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Withdrawal from long-term methamphetamine self-administration 'normalizes' neurometabolites in rhesus monkeys: a (1) H MR spectroscopy study.

Yang Shaolin S Belcher Annabelle M AM Chefer Svetlana S Vaupel D Bruce DB Schindler Charles W CW Stein Elliot A EA Yang Yihong Y

Addiction biology 20130804 1

(1) H magnetic resonance spectroscopy has demonstrated alterations in several neurometabolites in methamphetamine (METH)-dependent individuals in brain regions implicated in addiction. Yet, it is unclear whether these neurochemicals return to homeostatic levels after an individual abstains from drug use, a difficult question to address due to high recidivism and poor study retention in human subjects. We thus utilized a non-human primate model of addiction to explore the effects of long-term dru ...[more]

PMID: 23910722

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Dataset Information

Withdrawal from long-term methamphetamine self-administration 'normalizes' neurometabolites in rhesus monkeys: a (1) H MR spectroscopy study.

Publications

Withdrawal from long-term methamphetamine self-administration 'normalizes' neurometabolites in rhesus monkeys: a (1) H MR spectroscopy study.

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