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Original Article |
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Neuropsychopharmacology (1999) 21 427-434.10.1038/sj.npp.1395353
Effects of Repeated High-Dose Methamphetamine on Local Cerebral Glucose Utilization in Rats
Yn-Ho Huang1 Ph.D, Shih-Jen Tsai2,3 MD, Ting-Wen Su1 MSc and Cho-Boon Sim2 MD |
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1Institute and Department of Anatomy, National Yang-Ming University, Taipei, Taiwan, ROC
2Department of Psychiatry, Veterans General Hospital-Taipei, Taipei, Taiwan, ROC
3Division of Neuropsychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
Correspondence: Dr Yn-Ho Huang, Institute and Department of Anatomy, National Yang-Ming University, Taipei, Taiwan, ROC
This experiment was performed in the Cerebral Metabolism Laboratory, Institute and Department of Anatomy, National Yang-Ming University, Taiwan, ROC.
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ABSTRACT
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Repeated administration of high doses of methamphetamine (MAP) to rats can induce long-lasting neurotoxicity which may be related to permanent psychotic symptoms and negative symptoms in some MAP psychotic patients. In this study, we used the 2-[14C]deoxyglucose (2DG) method to analyze the effects of repeated MAP administration (12.5 mg/kg, i.p., 4 times every 2 hr within a day) 14 days and 60 days after drug administration. The results showed a wide-spread (26 of the 43 regions examined) decreases in the regional cerebral glucose utilization. The regions with decrease metabolism included all the extrapyramidal systems, the hippocampus formation and dorsal raphe nucleus. Rats tested 60 days after drug administration has similar finding to those with a 14-day abstinent period. The results of the functional change in this study provide support for the neurotoxic effects of repeated high dose MAP administration in rats. Furthermore, the neurotoxic effects are selective and long-lasting. We suggested the MAP neurotoxic model can be used to study the permanent psychosis and negative symptoms of MAP-induced psychosis in humans.
Keywords: Deoxyglucose; Methamphetamine; Neurotoxicity; Striatum; Rat |
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