THE TRICYCLIC ANTIDEPRESSANT CLOMIPRAMINE DOSE-DEPENDENTLY REDUCES REGIONAL CEREBRAL METABOLIC RATES FOR GLUCOSE 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 clomipramine (CMI), a serotonin (5-HT) uptake inhibitor and clinical antidepressant. rCMRglc was determined, using the quantitative autoradiographic [C-14]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 5HT(3) (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.