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Neuropharmacology. 2000;39(1):110-22.

Differential adaptation of brain 5-HT1A and 5-HT1B receptors and 5-HT transporter in rats treated chronically with fluoxetine.

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INSERM U288, NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, CHU Pitié-Salpêtrière, Paris, France.


Quantification of receptor binding sites and their encoding mRNAs, and electrophysiological recordings, were used to assess central serotonin (5-HT) neurotransmission in rats 24 h after a 2-3 week treatment with the selective 5-HT reuptake inhibitor fluoxetine (8 mg/kg i.p., daily). Binding studies showed that this treatment affected neither 5-HT1A nor 5-HT1B binding sites in all brain areas examined. However, a significant decrease (-38%) in 5-HT1A mRNA levels in the anterior raphe area (but not forebrain regions) and increases in 5-HT1B mRNA levels in the striatum (+127%) and the cerebral cortex (+34%) were noted in fluoxetine-treated rats. Electrophysiological recordings in brain slices showed that chronic fluoxetine treatment reduced the potency of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin to inhibit neuronal activity in the dorsal raphe nucleus, but did not affect 5-HT1A-evoked responses of CA1 pyramidal cells in the hippocampus. These data further demonstrate that fluoxetine-induced adaptive changes in 5-HT neurotransmission exhibit marked regional differences. The decrease in 5-HT1A mRNA levels in the anterior raphe suggests that fluoxetine-induced desensitization of 5-HT1A autoreceptors involves changes at the transcription level.

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