Differential adaptation of brain 5-HT1A and 5-HT1B receptors and 5-HT transporter in rats treated chronically with fluoxetine - PubMed (original) (raw)

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

E Le Poul et al. Neuropharmacology. 2000.

Abstract

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.

PubMed Disclaimer

Cited by

Decreased expression of Freud-1/CC2D1A, a transcriptional repressor of the 5-HT1A receptor, in the prefrontal cortex of subjects with major depression.
Szewczyk B, Albert PR, Rogaeva A, Fitzgibbon H, May WL, Rajkowska G, Miguel-Hidalgo JJ, Stockmeier CA, Woolverton WL, Kyle PB, Wang Z, Austin MC. Szewczyk B, et al. Int J Neuropsychopharmacol. 2010 Sep;13(8):1089-101. doi: 10.1017/S1461145710000301. Epub 2010 Apr 15. Int J Neuropsychopharmacol. 2010. PMID: 20392296 Free PMC article.
Acute treatment with the antidepressant fluoxetine internalizes 5-HT1A autoreceptors and reduces the in vivo binding of the PET radioligand [18F]MPPF in the nucleus raphe dorsalis of rat.
Riad M, Zimmer L, Rbah L, Watkins KC, Hamon M, Descarries L. Riad M, et al. J Neurosci. 2004 Jun 9;24(23):5420-6. doi: 10.1523/JNEUROSCI.0950-04.2004. J Neurosci. 2004. PMID: 15190115 Free PMC article.
Constitutive Serotonin Tone Modulates Molecular and Behavioral Response to Chronic Fluoxetine Treatment: A Study on Genetic Rat Model.
Kesić M, Mokrović G, Tvrdeić A, Miše B, Štefulj J, Čičin-Šain L. Kesić M, et al. Front Psychiatry. 2021 Oct 1;12:741222. doi: 10.3389/fpsyt.2021.741222. eCollection 2021. Front Psychiatry. 2021. PMID: 34658974 Free PMC article.
Omega-3 fatty acid deficiency does not alter the effects of chronic fluoxetine treatment on central serotonin turnover or behavior in the forced swim test in female rats.
McNamara RK, Able JA, Liu Y, Jandacek R, Rider T, Tso P, Lipton JW. McNamara RK, et al. Pharmacol Biochem Behav. 2013 Dec;114-115:1-8. doi: 10.1016/j.pbb.2013.09.010. Epub 2013 Oct 1. Pharmacol Biochem Behav. 2013. PMID: 24090922 Free PMC article.
Fluoxetine potentiation of methylphenidate-induced gene regulation in striatal output pathways: potential role for 5-HT1B receptor.
Van Waes V, Ehrlich S, Beverley JA, Steiner H. Van Waes V, et al. Neuropharmacology. 2015 Feb;89:77-86. doi: 10.1016/j.neuropharm.2014.08.024. Epub 2014 Sep 16. Neuropharmacology. 2015. PMID: 25218038 Free PMC article.

Differential adaptation of brain 5-HT1A and 5-HT1B receptors and 5-HT transporter in rats treated chronically with fluoxetine - PubMed (original) (raw)