Effect of 5-HT(1A) receptor antagonists on citalopram-induced increase in extracellular serotonin in the frontal cortex, striatum and dorsal hippocampus

R. Invernizzi, C. Velasco, M. Bramante, A. Longo, R. Samanin

Research output: Contribution to journalArticle

Abstract

The aim of the present study was to compare the effects of citalopram, either alone or combined with 5-HT(1A) receptor antagonists, on extracellular serotonin levels in brain regions innervated by the dorsal or median raphe nuclei. Using intracerebral microdialysis in awake rats with separate probes in the frontal cortex or dorsal hippocampus, we studied the ability of 8 mg/kg s.c. (-)penbutolol, a β-adrenoceptor antagonist with antagonist action at 5-HT(1A) and 5HT(1B) receptors, and 0.3 mg/kg s.c. WAY-100635, a selective 5-HT(1A) receptor blocker, to modify the effect of 1 and 10 mg/kg i.p. citalopram on extracellular serotonin. Both doses of citalopram had more effect on extracellular serotonin levels in the dorsal hippocampus than in the frontal cortex. The effect of 1 mg/kg citalopram was significantly potentiated by (-)penbutolol in the frontal cortex only, but a clear-cut potentiation of the effect of citalopram was seen in both regions at a dose of 10 mg/kg. The effect of 10 mg/kg citalopram was potentiated by WAY-100635 in the frontal cortex but not in the dorsal hippocampus. In a second set of experiments, the combined effect of WAY-100635 and citalopram was studied in the same rat implanted with vertical probes in the striatum and dorsal hippocampus. Citalopram (1 and 10 mg/kg i.p.) raised extracellular serotonin to a similar extent in both regions. However, 0.3 mg/kg s.c. WAY-100635 potentiated the effect of 10 mg/kg citalopram in the striatum but not in the dorsal hippocampus. The results suggest that only a combined blockade of 5-HT(1A) and 5-HT(1B) receptors potentiates the effect of citalopram on extracellular concentrations of serotonin in the dorsal hippocampus. The findings may be relevant in designing clinical trials aimed at enhancing the antidepressant action of selective serotonin re-uptake inhibitors by combining them with serotonin receptor antagonists.

Original languageEnglish
Pages (from-to)467-473
Number of pages7
JournalNeuropharmacology
Volume36
Issue number4-5
DOIs
Publication statusPublished - Apr 1997

Fingerprint

Citalopram
Receptor, Serotonin, 5-HT1A
Frontal Lobe
Hippocampus
Serotonin
Penbutolol
Receptor, Serotonin, 5-HT1B
Serotonin Antagonists
Raphe Nuclei
Microdialysis
Serotonin Uptake Inhibitors
Adrenergic Receptors
Antidepressive Agents
Clinical Trials

Keywords

  • 5-HT(1A) receptor
  • 5-HT(1B) receptor
  • Antidepressant activity
  • Dialysate 5-HT
  • Dorsal hippocampus
  • Frontal cortex
  • Microdialysis
  • SSRI
  • Striatum

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Effect of 5-HT(1A) receptor antagonists on citalopram-induced increase in extracellular serotonin in the frontal cortex, striatum and dorsal hippocampus. / Invernizzi, R.; Velasco, C.; Bramante, M.; Longo, A.; Samanin, R.

In: Neuropharmacology, Vol. 36, No. 4-5, 04.1997, p. 467-473.

Research output: Contribution to journalArticle

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