Time course of brain serotonin metabolism after cessation of long-term fluoxetine treatment in the rat.
The effects of repeated fluoxetine (Flx) administration (5, 10, or 15 mg/kg i.p., twice daily for 21 days) on serotonin and 5-HIAA metabolism were examined in the hypothalamus, hippocampus, pons medulla and cerebral cortex of rats killed 1-28 days after the last dose. Dose-dependent weight loss was observed during treatment, followed by gradual and complete recovery of body weight over the following two weeks. Chronic Flx treatment caused a dose-dependent decrease in brain 5-HT levels (by between 10 and 50% depending on the region examined), lasting for 3-7 days after cessation of treatment with the lowest and intermediate doses, and for 7-14 days after cessation of the highest dose. 5-HIAA levels decreased more markedly (-20; -60% depending on the region examined) than those of 5-HT, and tended to overshoot during the recovery period. The prolonged reduction in brain 5-HT levels after chronic Flx treatment was similar to that seen in rats given very high doses of dexfenfluramine (d-fen), a drug which both blocks 5-HT uptake and increases its release. These data suggest that brain 5-HT and 5-HIAA depletion may reflect similar dose-related expressions of the drug's mechanisms of action.
Trouvin
J H
JH
Fac. Pharmacie, Lab. Pharmacol, Catenay-Malabry, France.
Gardier
A M
AM
Chanut
E
E
Pages
N
N
Jacquot
C
C
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology* / Q000633:toxicity; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
D005473:Fluoxetine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid