title: Chronic 5-HT4 receptor agonist treatment restores learning and memory deficits in a neuroendocrine mouse model of anxiety/depression.
abstract: Cognitive disturbances are often reported as serious invalidating symptoms in patients suffering from major depression disorders (MDD) and are not fully corrected by classical monoaminergic antidepressant drugs. If the role of 5-HT4 receptor agonists as cognitive enhancers is well established in naïve animals or in animal models of cognitive impairment, their cognitive effects in the context of stress need to be examined. Using a mouse model of anxiety/depression (CORT model), we reported that a chronic 5-HT4 agonist treatment (RS67333, 1.5mg/kg/day) restored chronic corticosterone-induced cognitive deficits, including episodic-like, associative and spatial learning and memory impairments. On the contrary, a chronic monoaminergic antidepressant drug treatment with fluoxetine (18mg/kg/day) only partially restored spatial learning and memory deficits and had no effect in the associative/contextual task. These results suggest differential mechanisms underlying cognitive effects of these drugs. Finally, the present study highlights 5-HT4 receptor stimulation as a promising therapeutic mechanism to alleviate cognitive symptoms related to MDD.
authors: Université Paris-Saclay, Univ. Paris-Sud, Faculté de Pharmacie, CESP, INSERM UMRS1178, Chatenay-Malabry 92296, France.
authors: Flavie
authors: F
authors: Darcet
authors: Université Paris-Saclay, Univ. Paris-Sud, Faculté de Pharmacie, CESP, INSERM UMRS1178, Chatenay-Malabry 92296, France.
authors: Alain M
authors: AM
authors: Gardier
authors: Université Paris-Saclay, Univ. Paris-Sud, Faculté de Pharmacie, CESP, INSERM UMRS1178, Chatenay-Malabry 92296, France. Electronic address: denis.david@u-psud.fr.
authors: Denis J
authors: DJ
authors: David
authors: Université Paris-Saclay, Univ. Paris-Sud, Faculté de Pharmacie, CESP, INSERM UMRS1178, Chatenay-Malabry 92296, France. Electronic address: jean-philippe.guilloux@u-psud.fr.
authors: Jean-Philippe
authors: JP
authors: Guilloux
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology*; D001245:Association Learning / Q000187:drug effects; D003345:Corticosterone; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology*; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D007858:Learning / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D058828:Serotonin 5-HT4 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D065853:Spatial Learning / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D000814:Aniline Compounds; D000928:Antidepressive Agents; D003345:Corticosterone; D005473:Fluoxetine; D010880:Piperidines; D058828:Serotonin 5-HT4 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C107826:RS 67333
keywords: 5-HT(4) receptor agonist; Animal models of anxiety-depression; Cognitive deficits; Fluoxetine