Cerebral metabolic responses to clomipramine are greatly reduced following pretreatment with the specific serotonin neurotoxin para-chloroamphetamine (PCA). A 2-deoxyglucose study in rats.
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.
Freo
U
U
Clinica delle Malattie Nervose e Mentali, Padova, Italy.
Pietrini
P
P
Pizzolato
G
G
Furey
M
M
Merico
A
A
Ruggero
S
S
Dam
M
M
Battistin
L
L
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*
D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine; D003847:Deoxyglucose; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors; D010133:p-Chloroamphetamine