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.
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.
Authors: Vincent Beliveau; Claus Svarer; Vibe G Frokjaer; Gitte M Knudsen; Douglas N Greve; Patrick M Fisher Journal: Neuroimage Date: 2015-05-09 Impact factor: 6.556
Authors: Benjamin Adam Samuels; Indira Mendez-David; Charlène Faye; Sylvain André David; Kerri A Pierz; Alain M Gardier; René Hen; Denis J David Journal: Neuroscientist Date: 2014-12-08 Impact factor: 7.519
Authors: Alexandra Jean; Grégory Conductier; Christine Manrique; Constantin Bouras; Philippe Berta; René Hen; Yves Charnay; Joël Bockaert; Valérie Compan Journal: Proc Natl Acad Sci U S A Date: 2007-10-03 Impact factor: 11.205