Psychopharmacology

, Volume 221, Issue 2, pp 261–272

In vivo electrophysiological and neurochemical effects of the selective 5-HT1A receptor agonist, F13640, at pre- and postsynaptic 5-HT1A receptors in the rat

  • Laia Lladó-Pelfort
  • Marie-Bernadette Assié
  • Adrian Newman-Tancredi
  • Francesc Artigas
  • Pau Celada
Original Investigation

DOI: 10.1007/s00213-011-2569-9

Cite this article as:
Lladó-Pelfort, L., Assié, MB., Newman-Tancredi, A. et al. Psychopharmacology (2012) 221: 261. doi:10.1007/s00213-011-2569-9

Abstract

Rationale

F13640 (befiradol) is a novel 5-HT1A receptor agonist with exceptional selectivity vs. other receptors and binding sites. It shows analgesic activity in animal models and is currently developed for human use.

Objectives

Given the potential dual role of the serotonergic system in pain, through the modulation of ascending signals in spinal cord and their emotional processing by corticolimbic areas, we examined the in vivo activity of F13640 at somatodendritic autoreceptors and postsynaptic 5-HT1A heteroreceptors in medial prefrontal cortex (mPFC).

Methods

In vivo single unit recordings and intracerebral microdialysis in the rat.

Results

F13640 reduced the activity of dorsal raphe serotonergic neurons at 0.2–18.2 μg kg−1, i.v. (cumulative doses; ED50 = 0.69 μg kg−1, i.v.) and increased the discharge rate of 80% of mPFC pyramidal neurons in the same dose range (ED50 = 0.62 μg kg−1, i.v.). Both effects were reversed by the subsequent administration of the 5-HT1A receptor antagonist (±)WAY100635. In microdialysis studies, F13640 (0.04–0.63 mg kg−1, i.p.) dose-dependently decreased extracellular 5-HT in the hippocampus and mPFC. Likewise, F13640 (0.01–2.5 mg kg−1, i.p.) dose-dependently increased extracellular DA in mPFC, an effect dependent on the activation of postsynaptic 5-HT1A receptors in mPFC. Local perfusion of F13640 in mPFC (1–1,000 μM) also increased extracellular DA in a concentration-dependent manner. Both the systemic and local effects of F13640 were prevented by prior (±)WAY100635 administration.

Conclusions

These results indicate that, upon systemic administration, F13640 activates both 5-HT1A autoreceptors and postsynaptic 5-HT1A receptors in prefrontal cortex with a similar potency. Both activities are likely involved in the analgesic properties of the compound.

Keywords

5-HT1A receptorsDopaminePrefrontal cortexPyramidal neuronsSerotonin neurons

Abbreviations

DA

Dopamine

DR

Dorsal raphe nucleus

F13640

[(3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl}piperidin-1-yl]methanone Fumaric acid salt

mPFC

Medial prefrontal cortex

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Laia Lladó-Pelfort
    • 1
    • 2
  • Marie-Bernadette Assié
    • 3
  • Adrian Newman-Tancredi
    • 3
    • 5
  • Francesc Artigas
    • 1
    • 2
    • 4
  • Pau Celada
    • 1
    • 2
    • 4
  1. 1.Department of Neurochemistry and NeuropharmacologyInstitut d’Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPSBarcelonaSpain
  2. 2.Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)MadridSpain
  3. 3.Neurobiology Division 2Centre de Recherches Pierre FabreCastresFrance
  4. 4.Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)BarcelonaSpain
  5. 5.NeuroAct CommunicationCastresFrance