Yang Shaolin, Belcher Annabelle M, Chefer Svetlana, Vaupel D Bruce, Schindler Charles W, Stein Elliot A, Yang Yihong
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.
Addict Biol. 2015 Jan;20(1):69-79. doi: 10.1111/adb.12078. Epub 2013 Aug 4.
(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.
（1）氢磁共振波谱已证明，甲基苯丙胺（METH）依赖个体中，与成瘾相关的脑区有几种神经代谢物发生了改变。然而，尚不清楚个体戒毒后这些神经化学物质是否会恢复到稳态水平，由于人类受试者的高复发率和低研究保留率，这是一个难以解决的问题。因此，我们利用一种非人类灵长类动物成瘾模型，来探究长期药物暴露和戒断对脑神经化学的影响。十只恒河猴采用主动METH自我给药方案（平均使用4.6±0.8年，平均每日摄入量在0.4至1.2mg/kg之间），另外十只年龄和性别匹配的未接触过药物的对照猴（CONT）作为研究对象。在停止药物供应后的几个时间点评估了几种神经化学物质的浓度（10只猴子在1周、1个月和3个月时进行评估，6只猴子在6个月和12个月时进行评估；CONT在一个时间点进行检查）。在METH戒断后的1周，我们发现METH组前扣带回皮质中的肌醇相对于CONT有所增加。这些改变在戒断1年后呈现出水平下降的线性模式（“恢复正常”）。我们还发现，在戒断早期，同组动物的尾状核-壳核中的谷氨酰胺和Glx（主要由谷氨酸和谷氨酰胺组成）减少，且在1年后呈现出浓度增加的类似线性模式。这些结果表明，尽管长期、持续使用药物，但长期给药后出现的神经化学变化在长期戒断后并不会持续存在，这表明长期戒毒具有治疗效果。
