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

Quantification of receptor binding sites and their encoding mRNAs, and elec trophysiological recordings, were used to assess central serotonin (5-HT) n eurotransmission 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-H T1A mRNA levels in the anterior raphe area (but not forebrain regions) and increases in 5-HT1A mRNA levels in the striatum (+127%) and the cerebral co rtex (+34%) were noted in fluoxetine-treated rats. Electrophysiological rec ordings in brain slices showed that chronic fluoxetine treatment reduced th e potency of the 5HT(1A) agonist 8-hydroxy-2-(di-n-propyramino)tetralin to inhibit neuronal activity in the dorsal raphe nucleus, but did not affect 5 HT(1A)-evoked responses of CA1 pyramidal cells in the hippocampus. These da ta further demonstrate that fluoxetine-induced adaptive changes in 5-HT neu rotransmission exhibit marked regional differences. The decrease in 5-HT1A mRNA levels in the anterior raphe suggests that fluoxetine-induced desensit ization of 5-HT1A autoreceptors involves changes at the transcription level . (C) 1999 Published by Elsevier Science Ltd. All rights reserved.