title: Cerebral metabolic responses to clomipramine are greatly reduced following pretreatment with the specific serotonin neurotoxin para-chloroamphetamine (PCA). A 2-deoxyglucose study in rats.
abstract: To determine if reported reductions of regional cerebral metabolic rates for glucose (rCMRglc) induced by the tryciclic antidepressant clomipramine (CMI) (10 mg/kg) are due to a presynaptic action on serotonin (5-HT) terminals, 3-month-old Fischer-344 rats were given parachloroamphetamine (PCA), a serotonin neurotoxin. rCMRglc was measured 3 weeks later in 55 brain regions after the administration of saline or CMI using the quantitative autoradiographic [14C]2-deoxyglucose procedure. PCA alone increased rCMRglc in the visual cortex. CMI alone reduced rCMRglc in 18 (33%) of the studied regions, including telencephalic, diencephalic, limbic, and brain stem areas. In PCA-lesioned rats, metabolic responses to CMI (10 mg/kg) were greatly reduced, and significant rCMRglc decreases were observed only in 4 (7%) of the brain areas, including the hippocampus and raphe nuclei. Abolition by PCA of the metabolic responses to CMI confirms that CMI, at the dose studied, reduces rCMRglc via a presynaptic mechanism, likely the 5-HT reuptake sites.
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: G
authors.initials: G
authors.lastname: Pizzolato
authors.forename: M
authors.initials: M
authors.lastname: Furey
authors.forename: A
authors.initials: A
authors.lastname: Merico
authors.forename: S
authors.initials: S
authors.lastname: Ruggero
authors.forename: M
authors.initials: M
authors.lastname: Dam
authors.forename: L
authors.initials: L
authors.lastname: Battistin
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry; D002997:Clomipramine / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism*; D004734:Energy Metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D018490:Serotonin Agents / Q000008:administration & dosage*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D010133:p-Chloroamphetamine / Q000008:administration & dosage*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine; D003847:Deoxyglucose; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors; D010133:p-Chloroamphetamine