Metabolic mapping of the effects of intravenous methamphetamine administration in freely moving rats.
The 2-[14C]deoxyglucose method was used to examine the effects of acute intravenous administration of methamphetamine (0.5-2.5 mg/kg) on rates of local cerebral glucose utilization in freely-moving rats. These effects were correlated with the effects of methamphetamine on locomotor activity assessed simultaneously in the same animals. Methamphetamine administration resulted in widespread dose-dependent increases in glucose utilization within structures of the extrapyramidal motor system. Rates of glucose utilization were positively correlated with locomotor activity in the globus pallidus, substantia nigra reticulata, entopeduncular nucleus, subthalamic nucleus, and the lateral cerebellar cortex. In contrast, within the limbic system alterations in metabolic activity were smaller and more selective. Glucose utilization was increased in the nucleus accumbens at all doses tested, but alterations in glucose utilization in the ventral tegmental area, amygdala, and anterior cingulate were observed only at the highest doses of methamphetamine tested. Significant increases in rates of glucose metabolism were also found in the substantia nigra compacta and in the median and dorsal raphe nuclei. Dopamine and serotonin are depleted in these regions, as well as in the ventral tegmental area where glucose utilization was also increased, following chronic treatment with high doses of methamphetamine. These changes in glucose utilization may be indicative of disturbances in the biochemical processes involved in the neurotoxic effects of methamphetamine.
Pontieri
F E
FE
Laboratory of Cerebral Metabolism, National Institute of Mental Health, Public Health Service, Bethesda, MD 20892.
Crane
A M
AM
Seiden
L S
LS
Kleven
M S
MS
Porrino
L J
LJ
D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002245:Carbon Dioxide / Q000097:blood; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003847:Deoxyglucose; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D006400:Hematocrit; D007275:Injections, Intravenous; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D000697:Central Nervous System Stimulants; D002245:Carbon Dioxide; D008694:Methamphetamine; D003847:Deoxyglucose; D010100:Oxygen