1. Cerebral metabolic responses to clomipramine are greatly reduced following pretreatment with the specific serotonin neurotoxin para-chloroamphetamine (PCA). A 2-deoxyglucose study in rats.
- Author
-
Freo U, Pietrini P, Pizzolato G, Furey M, Merico A, Ruggero S, Dam M, and Battistin L
- Subjects
- Animals, Brain drug effects, Brain Chemistry, Energy Metabolism, Male, Rats, Rats, Inbred F344, Antidepressive Agents, Tricyclic pharmacology, Brain metabolism, Clomipramine pharmacology, Deoxyglucose metabolism, Serotonin Agents administration & dosage, Selective Serotonin Reuptake Inhibitors pharmacology, p-Chloroamphetamine administration & dosage
- 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.
- Published
- 1995
- Full Text
- View/download PDF