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Scientific article
English

Acute and chronic effects of citalopram on 5-HT1A receptor-labeling by [18F]MPPF and -coupling to receptors-G proteins

Contributors

Moulin-Sallanon, Marcelle; Charnay, Yves; Ginovart, Nathalie; Perret, Pascale; Lanfumey, Laurence; Hamon, Michel; Hen, René; Fagret, Daniel; Ibanez, Vicente; Millet, Philippe

Published in

Synapse, vol. 63, no. 2, p. 106-116

Publication date

2009

Abstract

Selective serotonin reuptake inhibitors take several weeks to produce their maximal therapeutic antidepressant effect. This delay has been attributed to the gradual desensitization of somatodendritic serotonin 5-HT(1A) autoreceptors. We evaluated adaptive changes of 5-HT(1A) receptors after acute and chronic citalopram challenges in rat. Small animal positron emission tomography trial and quantitative ex vivo autoradiography studies using [(18)F]MPPF were employed, as well as in vitro 8-OH-DPAT-stimulated [(35)S]-GTPgammaS binding assay. Additionally, 5-HT(1A) receptor knock-out mice were used to assess the specificity of [(18)F]MPPF. Acute treatment with citalopram did not alter [(18)F]MPPF binding in dorsal raphe nucleus (DR), frontal cortex, or hippocampus. The absence of [(18)F]MPPF binding in the brain of 5-HT(1A) knock-out mice demonstrates the specificity of MPPF for 5-HT(1A) receptor brain imaging, but the high affinity of [(18)F]MPPF compared to 5-HT suggests that it would only be displaced by dramatic increases in extracellular 5-HT. Chronic citalopram did not modify 5-HT(1A) receptor density in any of the brain regions studied. In addition, this treatment did not modify 8-OH-DPAT-stimulated [(35)S]-GTPgammaS binding in DR, although a significant increase was observed in frontal cortex and hippocampus. [(18)F]MPPF appears to be an efficient radioligand to quantify specifically 5-HT(1A) receptor density in brain imaging. The delayed therapeutic efficacy of citalopram did not appear to be linked to either a downregulation of 5-HT(1A) receptors or to a 5-HT(1A) receptor-G protein decoupling process in serotonergic neurons, but to increased functional sensitivity of postsynaptic 5-HT(1A) receptors.

Keywords

  • 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology
  • Animals
  • Autoradiography
  • Brain/*drug effects/metabolism/radionuclide imaging
  • Citalopram/*pharmacology
  • Fluorine Radioisotopes/diagnostic use
  • Guanosine 5'-O-(3-Thiotriphosphate)/metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Positron-Emission Tomography
  • Radiopharmaceuticals/diagnostic use
  • Rats
  • Rats, Wistar
  • Receptors, G-Protein-Coupled/*metabolism
  • Receptors, Serotonin, 5-HT1/genetics/*metabolism
  • Serotonin Receptor Agonists/pharmacology
  • Serotonin Uptake Inhibitors/*pharmacology

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

MOULIN-SALLANON, Marcelle et al. Acute and chronic effects of citalopram on 5-HT1A receptor-labeling by [18F]MPPF and -coupling to receptors-G proteins. In: Synapse, 2009, vol. 63, n° 2, p. 106–116. doi: 10.1002/syn.20588

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Additional URL for this publication

http://onlinelibrary.wiley.com/store/10.1002/syn.20588/asset/20588_ftp.pdf?v=1&t=gzs5n9hn&s=9831103e3c6077a1489da164352f4a88fe8cdc6a

Journal ISSN

0887-4476
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Technical informations

Creation

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First validation

23/04/2012 13:24:31

Update

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