Selective alterations in cerebral metabolism within the mesocorticolimbic dopaminergic system produced by acute cocaine administration in rats.
The 2-[14C]deoxyglucose method was used to examine the effects of acute intravenous administration of cocaine on local cerebral glucose utilization in rats. These effects were correlated with the effects of cocaine on locomotor activity assessed simultaneously in the same animals. At the lowest dose of cocaine, 0.5 mg/kg (1.47 mumol/kg), alterations in glucose utilization were restricted to the medial prefrontal cortex and nucleus accumbens. Metabolic activity at 1.0 mg/kg (2.9 mumol/kg) was altered in these structures, but in the substantia nigra reticulata and lateral habenula as well. The selectivity of cocaine's effects at low doses demonstrates the particular sensitivity of these structures to cocaine's actions in the brain. In contrast, 5.0 mg/kg (14.7 mumol/kg) produced widespread changes in glucose utilization, particularly in the extrapyramidal system. Only this dose significantly increased locomotor activity above levels in vehicle-treated controls. Rates of glucose utilization were positively correlated with locomotor activity in the globus pallidus, substantia nigra reticulata, and subthalamic nucleus, and negatively correlated in the lateral habenula.
Porrino
L J
LJ
Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224.
Domer
F R
FR
Crane
A M
AM
Sokoloff
L
L
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology*; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006400:Hematocrit; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009928:Organ Specificity; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D003837:Deoxy Sugars; D003847:Deoxyglucose; D003042:Cocaine