title: Region-dependent regulation of mesoaccumbens dopamine neurons in vivo by the constitutive activity of central serotonin2C receptors.
abstract: Central serotonin2C receptors (5-HT(2C)Rs) control the mesoaccumbens dopamine (DA) pathway. This control involves the constitutive activity (CA) of 5-HT(2C)Rs, and is thought to engage regionally distinct populations of 5-HT(2C)Rs, leading to opposite functional effects. Here, using in vivo microdialysis in halothane-anesthetized rats, we investigated the relative contribution of ventral tegmental area (VTA) and nucleus accumbens shell (NAc) 5-HT(2C)Rs in the phasic/tonic control of accumbal DA release, to specifically identify the nature (inhibition/excitation) of the control, and the role of the 5-HT(2C)R CA. Intra-VTA injections of the selective 5-HT(2C)R antagonists SB 242084 and/or SB 243213 (0.1-0.5 microg/0.2 microL) prevented the decrease in accumbal DA outflow induced by the 5-HT(2C)R agonist Ro 60-0175 (3 mg/kg, i.p), but did not affect the increase in DA outflow induced by the 5-HT(2C)R inverse agonist SB 206553 (5 mg/kg, i.p). Intra-NAc infusions of SB 242084 (0.1-1 microM) blocked Ro 60-0175- and SB 206553-induced changes of DA outflow. Intra-NAc, but not intra-VTA administration of SB 206553 increased basal DA outflow. These findings demonstrate that both VTA and NAc 5-HT(2C)Rs participate in the inhibitory control exerted by 5-HT(2C)Rs on accumbal DA release, and that the NAc shell may represent a primary action site for the CA of 5-HT(2C)Rs.
authors.affiliation: Unité Mixte de Recherche-Centre National de la Recherche Scientifique (UMR-CNRS 5541), Université Victor Segalen Bordeaux 2, 146 rue Léo Saignât, Boîte Postale 31, 33076 Bordeaux Cedex, France.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Navailles
authors.forename: Delphine
authors.initials: D
authors.lastname: Moison
authors.forename: Dimitri
authors.initials: D
authors.lastname: Ryczko
authors.forename: Umberto
authors.initials: U
authors.lastname: Spampinato
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D004298:Dopamine