title: The tricyclic antidepressant clomipramine dose-dependently reduces regional cerebral metabolic rates for glucose 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 clomipramine (CMI), a serotonin (5-HT) uptake inhibitor and clinical antidepressant. rCMRglc was determined, using the quantitative autoradiographic [14C]2-deoxyglucose technique, in 64 brain regions at 20, 40, 60, 120, and 180 min after administration of CMI 50 mg/kg IP and 120 min after CMI 2 and 10 mg/kg IP. The peak metabolic effect was observed at 120 min after CMI. At that time, CMI 2 and 10 mg/kg IP significantly reduced rCMRglc from control values in 12 (19%) and 14 (22%) brain regions, which correspond to areas with high densities of 5-HT reuptake sites (e.g. visual and limbic areas and raphe nuclei). CMI 50 mg/kg produced widespread rCMRglc reductions in 34 (53%) brain regions, including cortical, hippocampal, raphe and cerebellar areas. The topographic distribution and the relation to time and dose of CMI effects on rCMRglc are different from those of 5-HT1A [8-hydroxy-2(di-N-propylamino) tetralin], 5-HT1B-C (m-chlorophenylpiperazine) and 5-HT3 (quipazine) agonists and resemble those produced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), an agonist of 5-HT2 receptors, suggesting that CMI may prefentially stimulate this 5-HT receptor subtype.
authors.affiliation: Clinica delle Malattie Nervose e Mentali, Padova, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Freo
authors.forename: P
authors.initials: P
authors.lastname: Pietrini
authors.forename: M
authors.initials: M
authors.lastname: Dam
authors.forename: G
authors.initials: G
authors.lastname: Pizzolato
authors.forename: L
authors.initials: L
authors.lastname: Battistin
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology; D001923:Brain Chemistry / Q000187:drug effects*; D001931:Brain Mapping; D002997:Clomipramine / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D007700:Kinetics; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D003847:Deoxyglucose; D005947:Glucose; D002997:Clomipramine