title: (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: National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Yi
authors: Y
authors: Deng
authors: Qian
authors: Q
authors: Bu
authors: Zhengtao
authors: Z
authors: Hu
authors: Pengchi
authors: P
authors: Deng
authors: Guangyan
authors: G
authors: Yan
authors: Jiachuan
authors: J
authors: Duan
authors: Chunyan
authors: C
authors: Hu
authors: Jiaqing
authors: J
authors: Zhou
authors: Xue
authors: X
authors: Shao
authors: Jinxuan
authors: J
authors: Zhao
authors: Yan
authors: Y
authors: Li
authors: Ruiming
authors: R
authors: Zhu
authors: Yinglan
authors: Y
authors: Zhao
authors: Xiaobo
authors: X
authors: Cen
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008253:Macaca mulatta; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D008691:Methadone / Q000494:pharmacology; D009020:Morphine / Q000009:adverse effects; D009021:Morphine Dependence / Q000378:metabolism*; D009294:Narcotics / Q000009:adverse effects; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
chemical_list: D009294:Narcotics; D009020:Morphine; D008691:Methadone