DOSE-DEPENDENT AND TIME-DEPENDENT EFFECTS OF 1-(2,5-DIMETHOXY-4-IODOPHENYL)-2-AMINOPROPANE (DOI), A SEROTONERGIC 5-HT2 RECEPTOR AGONIST, ON LOCAL CEREBRAL GLUCOSE-METABOLISM IN AWAKE RATS

The time course and the relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male Fischer-344 rats after administration of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective serotonergic 5-HT2 agonist. rCMRglc was determined, using the quantitative autoradiographic [C-14]2-deoxyglucose technique, in 75 brain regions at 5, 15, 30, 60 and 90 min after administration of DOI 10 mg/kg i.p., and at 15 min after DOI 2.5, 25 or 50 mg/kg i.p. In non-hippocampal regions, peak effects were observed at 15-30 min, when rCMRglc in 12% of the regions was significantly different from control. In hippocampal regions rCMRglc effects peaked at 30 min (average rCMRglc reduction 21%) and were sustained for at least 60 min. Higher doses of DOI reduced rCMRglc in most prosencephalic regions (25 mg/kg, 35% of all regions studied; 50 mg/kg, 32%), where 5-HT2 receptors are present in high density. These data suggest that selective 5-HT2 receptor stimulation leads to rCMRglc reduction in areas with high densities of 5-HT2 receptors.