Effects of repeated high-dose methamphetamine on local cerebral glucose utilization in rats

Repeated administration of high doses of methamphetamine (MAP) to rats can induce long-lasting neurotoxicity which may be related to permanent psychot ic symptoms and negative symptoms in some MAP psychotic patients. In this s tudy, we used the 2-[C-14]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 widespread (26 of the 43 regions examined) decreases in the regional cereb ral glucose utilization. The regions with decrease metabolism included all the extrapyramidal systems, the hippocampus formation and dorsal raphe nucl eus. Rats tested 60 days after drug administration has similar finding to t hose with a 14-day abstinent period. The results of the functional change i n this study provide support for the neurotoxic effects of repented high do se MAP administration in mts. Furthermore, the neurotoxic effects are selec tive and long-lasting. We suggested the MAP neurotoxic model can be used to study the permanent psychosis and negative symptoms of MAP-induced psychos is in humans. (C) 1999 American College of Neuropsychopharmacology. Publish ed by Elsevier Science Inc.