title: NMR-based metabonomic in hippocampus, nucleus accumbens and prefrontal cortex of methamphetamine-sensitized rats.
abstract: (1)H NMR spectroscopy was applied to investigate the changes of cerebral metabolites in brain hippocampus, nucleus accumbens (NAC) and prefrontal cortex (PFC) of the rats subjected to subcutaneous twice-daily injections of 2.5mg/kg methamphetamine (MAP) for 7 days. The results indicated that MAP exposure induced significant behavioral sensitization and altered cerebral metabolites in rats. The neurotransmitters glutamate, glutamine and GABA significantly decreased in hippocampus, NAC and PFC. Specifically, increased succinic acid semialdehyde, a metabolism product of GABA, was observed in hippocampus. Additionally, decreased serotonin was observed in both NAC and PFC, whereas decreased dopamine was only observed in NAC after repeated MAP treatment. Glutathione obviously decreased in above brain regions, whereas acetylcysteine declined in hippocampus and NAC, and taurine declined in NAC and PFC. Homocysteic acid was elevated in hippocampus and NAC by repeated MAP administration. Membrane ingredients like phosphocholine elevated in response to MAP administration in NAC and PFC. N-Acetyl-aspartate, a marker of neuronal viability, decreased in the three regions; however, myo-inositol, a glial cell marker, increased in hippocampus and PFC. Tricarboxylic acid cycle intermediate products, such as α-ketoglutarate, succinate, citrate and the methionine significantly decreased in above three brain regions after MAP administration; however, ADP decreased in hippocampus. These results indicate that repeated MAP treatment causes neurotransmitters disturbance, imbalance between oxidative stress and antioxidants, and gliosis in hippocampus, NAC and PFC. Profound metabolic changes detected across brain regions provide the first evidence of metabonomic changes in MAP-induced sensitized rats.
authors: National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors: Qian
authors: Q
authors: Bu
authors: Lei
authors: L
authors: Lv
authors: Guangyan
authors: G
authors: Yan
authors: Pengchi
authors: P
authors: Deng
authors: Yanli
authors: Y
authors: Wang
authors: Jiaqing
authors: J
authors: Zhou
authors: Yanzhu
authors: Y
authors: Yang
authors: Yan
authors: Y
authors: Li
authors: Xiaobo
authors: X
authors: Cen
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D059333:Central Nervous System Sensitization / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D016002:Discriminant Analysis; D004195:Disease Models, Animal; D006624:Hippocampus; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D008694:Methamphetamine / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D009714:Nucleus Accumbens; D017397:Prefrontal Cortex; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium
chemical_list: D000697:Central Nervous System Stimulants; D018377:Neurotransmitter Agents; D014316:Tritium; D008694:Methamphetamine