(1) H-nuclear magnetic resonance-based metabonomic analysis of brain in rhesus monkeys with morphine treatment and withdrawal intervention.

Abstract

Comprehensive cerebral metabolites involved in morphine dependence have not been well explored. To gain a better understanding of morphine dependence and withdrawal therapy in a model highly related to humans, metabolic changes in brain hippocampus and prefrontal cortex (PFC) of rhesus monkeys were measured by (1) H-nuclear magnetic resonance spectroscopy, coupled with partial least squares and orthogonal signal correction analysis. The results showed that concentrations of myoinositol (M-Ins) and taurine were significantly reduced, whereas lactic acid was increased in hippocampus and PFC of morphine-dependent monkeys. Phosphocholine and creatine increased in PFC but decreased in hippocampus after chronic treatment of morphine. Moreover, N-acetyl aspartate (NAA), γ-aminobutyric acid, glutamate, glutathione, methionine, and homocysteic acid also changed in these brain regions. These results suggest that chronic morphine exposure causes profound disturbances of neurotransmitters, membrane, and energy metabolism in the brain. Notably, morphine-induced dysregulations in NAA, creatine, lactic acid, taurine, M-Ins, and phosphocholine were clearly reversed after intervention with methadone or clonidine. Our study highlights the potential of metabolic profiling to enhance our understanding of metabolite alteration and neurobiological actions associated with morphine addiction and withdrawal therapy in primates.

• Authors: Yi Deng, Qian Bu, Zhengtao Hu, Pengchi Deng, Guangyan Yan, Jiachuan Duan, Chunyan Hu, Jiaqing Zhou, Xue Shao, Jinxuan Zhao, Yan Li, Ruiming Zhu, Yinglan Zhao, Xiaobo Cen
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 90 Issue 11 Pg. 2154-62 (Nov 2012) ISSN: 1097-4547 [Electronic] United States
• PMID: 22847893 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Narcotics
• Morphine
• Methadone

Topics

• Animals
• Brain (drug effects, metabolism)
• Disease Models, Animal
• Female
• Macaca mulatta
• Magnetic Resonance Spectroscopy
• Male
• Metabolomics
• Methadone (pharmacology)
• Morphine (adverse effects)
• Morphine Dependence (metabolism)
• Narcotics (adverse effects)
• Substance Withdrawal Syndrome (metabolism)