Time- and dose-dependent effects of the serotonergic agent quipazine on regional cerebral metabolism in rats.
The time course and the relation to dose of regional cerebral metabolic rates for glucose (rCMRglc) were measured in awake male adult Fischer-344 rats after administration of quipazine, a serotonin 5-HT2-3 receptor agonist. rCMRglc was determined, using the quantitative autoradiographic [14C]deoxyglucose technique, in 92 brain regions at 30, 60, 90 and 120 min after quipazine 20 mg/kg i.p. and at 60 min after quipazine 5 mg/kg i.p. Peak metabolic effects were observed 60 min after quipazine 20 mg/kg i.p. when rCMRglc was significantly elevated in 27 (29%) brain regions (mean rise 17%). Quipazine increased rCMRglc in brain regions with high densities of 5-HT3 receptors (area postrema, olfactory tubercle, amygdala), in dopaminergic nuclei (substantia nigra pars compacta and pars reticulata) and terminal fields of their projections (zona incerta, subthalamic nucleus, preoptic magnocellular area, nucleus of facial nerve). The topographic distribution and direction of rCMRglc changes induced by quipazine are different from those produced by the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and, consistent with the pharmacological and binding properties of quipazine, suggest a preferential activation of 5-HT3 receptors.
Freo
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Unit on Pharmacology and Pharmacokinetics, National Institutes on Aging, National Institutes of Health, Bethesda, MD 20892.
Ricchieri
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GL
Holloway
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HW
Soncrant
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TT
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects*; D003847:Deoxyglucose; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D011814:Quipazine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013997:Time Factors
D000662:Amphetamines; D017366:Serotonin Receptor Agonists; D011814:Quipazine; D003847:Deoxyglucose; D005947:Glucose; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine