101. Frontocortical 5-HT4 receptors exert positive feedback on serotonergic activity: viral transfections, subacute and chronic treatments with 5-HT4 agonists
- Author
-
Eric J. Nestler, Valérie Compan, Michel Barrot, Guillaume Lucas, Guy Debonnel, Yves Charnay, Rachael L. Neve, Joël Bockaert, Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Rodeau, Jean-Luc, Institut cellule souche et cerveau (U846 Inserm - UCBL1), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Hôpitaux Universitaires de Genève (HUG), Department of Psychiatry, McLean Hospital, Department of Psychiatry [Montréal], and McGill University = Université McGill [Montréal, Canada]
- Subjects
Male ,Indoles ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Herpesvirus 1, Human ,Striatum ,Rats, Sprague-Dawley ,0302 clinical medicine ,Piperidines ,Receptor ,In Situ Hybridization ,ComputingMilieux_MISCELLANEOUS ,Neurons ,Sulfonamides ,0303 health sciences ,Aniline Compounds ,Pyramidal Cells ,Gene Transfer Techniques ,Iontophoresis ,Receptor antagonist ,musculoskeletal system ,Frontal Lobe ,Serotonin Receptor Agonists ,Electrophysiology ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Serotonin Antagonists ,Serotonin ,medicine.medical_specialty ,medicine.drug_class ,Genetic Vectors ,Serotonergic ,Feedback ,03 medical and health sciences ,Dorsal raphe nucleus ,Internal medicine ,medicine ,Animals ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Biological Psychiatry ,5-HT receptor ,Benzofurans ,030304 developmental biology ,business.industry ,RNA Probes ,Rats ,Endocrinology ,Raphe Nuclei ,Receptors, Serotonin, 5-HT4 ,Extracellular Space ,Raphe nuclei ,business ,030217 neurology & neurosurgery - Abstract
International audience; BACKGROUND: We recently identified a facilitory control exerted by serotonin4 (5-HT4) receptors on the in vivo firing activity of dorsal raphe nucleus (DRN) serotonergic (5-HT) neurons. However, these findings were based on acute administrations of 5-HT4 receptor agonists and antagonists, which were active only in a subpopulation of 5-HT neurons. We had no evidence that this influence was significant when considering the entire DRN, nor if it was persistent after chronic treatments. In addition, the poor distribution of 5-HT4 receptors within the DRN raised the question of the neuroanatomical bases underlying this control. METHODS AND RESULTS: Here we show that the subacute intraperitoneal (IP) injection of the 5-HT4 receptor agonists prucalopride (2.5 mg/kg) and RS 67333 (1.5 mg/kg) 30 minutes before the beginning of recordings augment the mean firing rate of DRN neurons by 40% and 66%, respectively. These increases remain stable when the compounds are administered continuously during 3 and 21 days; the effects of the 3-day treatment are blocked by the 5-HT4 receptor antagonist GR 125487 (1000 microg/kg, intravenous [i.v.]). In addition, stereotaxic microinjections of herpes simplex viruses, transformed to overexpress 5-HT4 receptors, increase DRN 5-HT neuronal mean activity when performed in the medial prefrontal cortex (mPFC) but not in the striatum or in the hippocampus. CONCLUSIONS: This finding suggests the existence of a 5-HT(4)-dependent activation of DRN that may involve the mPFC, unveiling the 5-HT4 receptor as a putative player in the physiopathology of several disorders related to central 5-HT dysfunction.
- Published
- 2005