title: In vivo evidence that constitutive activity of serotonin2C receptors in the medial prefrontal cortex participates in the control of dopamine release in the rat nucleus accumbens: differential effects of inverse agonist versus antagonist.
abstract: Control of the mesoaccumbens dopamine (DA) pathway by central serotonin(2C) receptors (5-HT(2C)Rs) involves different 5-HT(2C)R populations located within multiple brain areas. Here, using in vivo microdialysis in halothane-anesthetized rats, we assessed the role of medial prefrontal cortex (mPFC) 5-HT(2C)Rs in the control of basal and activated accumbal DA outflow, to identify the modalities of their recruitment and the role of 5-HT(2C)R constitutive activity. Intra-mPFC injection of the 5-HT(2C)R inverse agonist SB 206553 (0.5 microg/0.2 microL), without effect by itself, decreased accumbal DA outflow induced by morphine (2.5-10 mg/kg, s.c.), haloperidol (0.01 mg/kg, s.c.) or GBR 12909 (2.5 mg/kg, i.p.). Conversely, intra-mPFC injection of the 5-HT(2C)R antagonist SB 242084 (0.5 microg/0.2 microL), without effect by itself, decreased the effect of 10 mg/kg morphine, the only drug enhancing basal 5-HT outflow in the mPFC. The inhibitory effect of SB 206553 on 2.5 mg/kg morphine-stimulated DA outflow was suppressed by the concomitant intra-mPFC injection of SB 242084. Finally, changes of basal DA outflow induced by the 5-HT(2C)R agonist Ro 60-0175 (3 mg/kg, i.p.) or SB 206553 (5 mg/kg, i.p.) were unaffected by intra-mPFC injection of SB 242084. These results, showing that 5-HT(2C)R antagonist and inverse agonist behave differently in vivo, demonstrate that mPFC 5-HT(2C)Rs facilitate activated accumbal DA outflow and that 5-HT(2C)R constitutive activity participates in this interaction.
authors.affiliation: Inserm U862, Neurocentre Magendie, Physiopathology of Addiction group, Bordeaux F-33000, France.
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Leggio
authors.forename: Adeline
authors.initials: A
authors.lastname: Cathala
authors.forename: Maud
authors.initials: M
authors.lastname: Neny
authors.forename: Françoise
authors.initials: F
authors.lastname: Rouge-Pont
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.forename: Pier Vincenzo
authors.initials: PV
authors.lastname: Piazza
authors.forename: Umberto
authors.initials: U
authors.lastname: Spampinato
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005021:Ethylamines / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D009019:Morphinans / Q000494:pharmacology; D009434:Neural Pathways / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D000701:Analgesics, Opioid; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D005021:Ethylamines; D007211:Indoles; D009019:Morphinans; D010879:Piperazines; D011725:Pyridines; D044405:Receptor, Serotonin, 5-HT2C; C103848:Ro 60-0175; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C495883:morphinandienone; C043425:vanoxerine; C094868:SB 206553; D006220:Haloperidol; D004298:Dopamine