Strain-dependent serotonin neuron feedback control

Role of serotonin 2C receptors

Eleonora Calcagno, Roberto W. Invernizzi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We investigated the role of serotonin2C receptor-mediated feedback mechanisms in the response to citalopram in C57BL/6 and DBA/2 mice, which are respectively responders and non-responders to selective serotonin reuptake inhibitors in the forced swimming test. The microdialysis technique was used to assess changes in extracellular serotonin and GABA in the mouse dorsal raphé (DR). Citalopram (1.25-20 mg/kg) raised extracellular serotonin and GABA in the DR of both mouse strains. These effects were abolished by depleting brain serotonin with p-chlorophenylalanine (300 mg/kg × 3). Systemic and/or intra-DR infusion of the serotonin2C receptor antagonist 6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline (1 mg/kg and 0.1 μM, respectively) enhanced citalopram's effect on extracellular serotonin in the DR and medial prefrontal cortex and abolished the rise of GABA in the DR of DBA/2 mice but had no effect in C57BL/6 mice. The serotonin2C receptor agonist Ro60-0175 (0.03-3.0 mg/kg) reduced extracellular serotonin and raised GABA in the DR of DBA/2 mice but had much less effect in C57BL/6 mice. These findings show that the sensitivity of serotonin2C receptors determines the efficacy of augmentation strategies aimed at enhancing the effect of serotonin reuptake inhibitors on extracellular serotonin through the suppression of serotonin2C receptor-mediated feedback control of serotonin neurons.

Original languageEnglish
Pages (from-to)1701-1710
Number of pages10
JournalJournal of Neurochemistry
Volume114
Issue number6
DOIs
Publication statusPublished - 2010

Fingerprint

Receptor, Serotonin, 5-HT2C
Neurons
Feedback control
Serotonin
Citalopram
gamma-Aminobutyric Acid
Inbred DBA Mouse
Serotonin Uptake Inhibitors
Inbred C57BL Mouse
Fenclonine
Microdialysis
Prefrontal Cortex
Brain
Feedback

Keywords

  • dorsal raphé
  • GABA
  • mouse strain
  • serotonin
  • SSRIs

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Strain-dependent serotonin neuron feedback control : Role of serotonin 2C receptors. / Calcagno, Eleonora; Invernizzi, Roberto W.

In: Journal of Neurochemistry, Vol. 114, No. 6, 2010, p. 1701-1710.

Research output: Contribution to journalArticle

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