title: 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.
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA; Departments of Psychiatry, Radiology, and Bioengineering, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Shaolin
authors.initials: S
authors.lastname: Yang
authors.forename: Annabelle M
authors.initials: AM
authors.lastname: Belcher
authors.forename: Svetlana
authors.initials: S
authors.lastname: Chefer
authors.forename: D Bruce
authors.initials: DB
authors.lastname: Vaupel
authors.forename: Charles W
authors.initials: CW
authors.lastname: Schindler
authors.forename: Elliot A
authors.initials: EA
authors.lastname: Stein
authors.forename: Yihong
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D005973:Glutamine / Q000187:drug effects / Q000378:metabolism; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D008137:Longitudinal Studies; D008253:Macaca mulatta; D008694:Methamphetamine / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D005973:Glutamine; D018698:Glutamic Acid; D008694:Methamphetamine; D007294:Inositol
keywords: Abstinence; glutamate; glutamine; magnetic resonance spectroscopy; methamphetamine; rhesus monkey
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