Dose- 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 [14C]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.
Freo
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Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892.
Soncrant
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Holloway
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Rapoport
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D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors; D014018:Tissue Distribution; D014851:Wakefulness
D000662:Amphetamines; D012702:Serotonin Antagonists; D005947:Glucose; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine