%P 53-59
%J Psychopharmacology
%R 10.1007/BF02244334
%T The tricyclic antidepressant clomipramine dose-dependently reduces regional cerebral metabolic rates for glucose in awake rats
%N 1
%V 113
%D 1993
%A Ulderico Freo
%A Pietro Pietrini
%A Mario Damiano
%A Gilberto Pizzolato
%A Leontino Battistin
%I Springer
%L eprints3331
%X 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 14C2-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.
%K Clomipramine; Serotonin; Rats; Brain; Metabolism