title: 5-HT(2C) serotonin receptor blockade prevents tau protein hyperphosphorylation and corrects the defect in hippocampal synaptic plasticity caused by a combination of environmental stressors in mice.
abstract: Exposure to multimodal sensory stressors is an everyday occurrence and sometimes becomes very intense, such as during rave parties or other recreational events. A growing body of evidence suggests that strong environmental stressors might cause neuronal dysfunction on their own in addition to their synergistic action with illicit drugs. Mice were exposed to a combination of physical and sensory stressors that are reminiscent of those encountered in a rave party. However, this is not a model of rave because it lacks the rewarding properties of rave. A 14-h exposure to environmental stressors caused an impairment of hippocampal long-term potentiation (LTP) and spatial memory, and an enhanced phosphorylation of tau protein in the CA1 and CA3 regions. These effects were transient and critically depended on the activation of 5-HT2C serotonin receptors, which are highly expressed in the CA1 region. Acute systemic injection of the selective 5-HT2C antagonist, RS-102,221 (2 mg/kg, i.p., 2 min prior the onset of stress), prevented tau hyperphosphorylation and also corrected the defects in hippocampal LTP and spatial memory. These findings suggest that passive exposure to a combination of physical and sensory stressors causes a reversible hippocampal dysfunction, which might compromise mechanisms of synaptic plasticity and spatial memory for a few days. Drugs that block 5-HT2C receptors might protect the hippocampus against the detrimental effect of environmental stressors.
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, 86077 Pozzilli, Italy. Electronic address: carla.busceti@neuromed.it.
authors.forename: Carla Letizia
authors.initials: CL
authors.lastname: Busceti
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, 86077 Pozzilli, Italy. Electronic address: p.dipietro06@virgilio.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Di Pietro
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, 86077 Pozzilli, Italy. Electronic address: barbara.riozzi@neuromed.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Riozzi
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, 86077 Pozzilli, Italy. Electronic address: annatraficante@yahoo.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Traficante
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, 86077 Pozzilli, Italy. Electronic address: frbiagioni@libero.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Biagioni
authors.affiliation: Department of Physiology and Pharmacology, University "Sapienza", Piazzale Aldo Moro, 5, 00185 Rome, Italy; European Brain Research Institute, Via del Fosso di Fiorano, 64, 00143 Rome, Italy. Electronic address: robert.nistico@gmail.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Nisticò
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, 86077 Pozzilli, Italy; Department of Human Morphology and Applied Biology, University of Pisa, Via Savi 10, 56126 Pisa, Italy. Electronic address: francesco.fornai@med.unipi.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fornai
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, 86077 Pozzilli, Italy. Electronic address: giuseppe.battaglia@neuromed.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, 86077 Pozzilli, Italy; Department of Physiology and Pharmacology, University "Sapienza", Piazzale Aldo Moro, 5, 00185 Rome, Italy. Electronic address: ferdinandonicoletti@hotmail.com.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, Località Camerelle, 86077 Pozzilli, Italy; Department of Physiology and Pharmacology, University "Sapienza", Piazzale Aldo Moro, 5, 00185 Rome, Italy. Electronic address: valeria.bruno@uniroma1.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Bruno
mesh_terms: D000818:Animals; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D013312:Stress, Physiological / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists; D016875:tau Proteins
keywords: MDMA; Memory retrival; Serotonin; Synaptic plasticity; Tau protein