title: 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.
abstract: 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.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892.
authors.forename: U
authors.initials: U
authors.lastname: Freo
authors.forename: T T
authors.initials: TT
authors.lastname: Soncrant
authors.forename: H W
authors.initials: HW
authors.lastname: Holloway
authors.forename: S I
authors.initials: SI
authors.lastname: Rapoport
mesh_terms: 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
chemical_list: D000662:Amphetamines; D012702:Serotonin Antagonists; D005947:Glucose; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine