title: Presynaptic CB(1) cannabinoid receptors control frontocortical serotonin and glutamate release--species differences.
abstract: Both the serotonergic and endocannabinoid systems modulate frontocortical glutamate release; thus they are well positioned to participate in the pathogenesis of psychiatric disorders. With the help of fluorescent and confocal microscopy, we localized the CB(1) cannabinoid receptor (CB(1)R) in VGLUT1- and 2- (i.e. glutamatergic) and serotonin transporter- (i.e. serotonergic) -positive fibers and nerve terminals in the mouse and rat frontal cortex. CB(1)R activation by the synthetic agonists, WIN55212-2 (1 μM) and R-methanandamide (1 μM) inhibited the simultaneously measured evoked Ca(2+)-dependent release of [(14)C]glutamate and [(3)H]serotonin from frontocortical nerve terminals of Wistar rats, in a fashion sensitive to the CB(1)R antagonists, O-2050 (1 μM) and LY320135 (5 μM). CB(1)R agonists also inhibited the evoked release of [(14)C]glutamate in C57BL/6J mice in a reversible fashion upon washout. Interestingly, the evoked release of [(14)C]glutamate and [(3)H]serotonin was significantly greater in the CB(1)R knockout CD-1 mice. Furthermore, CB(1)R binding experiments revealed similar frontocortical CB(1)R density in the rat and the CD-1 mouse. Still, the evoked release of [(3)H]serotonin was modulated by neither CB(1)R agonists nor antagonists in wild-type CD-1 or C57BL/6J mice. Altogether, this is the first study to demonstrate functional presynaptic CB(1)Rs in frontocortical glutamatergic and serotonergic terminals, revealing species differences.
authors.affiliation: Center for Neuroscience and Cell Biology of Coimbra, Faculty of Medicine, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Samira G
authors.initials: SG
authors.lastname: Ferreira
authors.forename: Filipe M
authors.initials: FM
authors.lastname: Teixeira
authors.forename: Pedro
authors.initials: P
authors.lastname: Garção
authors.forename: Paula
authors.initials: P
authors.lastname: Agostinho
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.forename: Luísa
authors.initials: L
authors.lastname: Cortes
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
authors.forename: Attila
authors.initials: A
authors.lastname: Köfalvi
mesh_terms: D000818:Animals; D005971:Glutamates / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010880:Piperidines / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D011720:Pyrazoles / Q000378:metabolism; D011786:Quality Control; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism*; D000077285:Rimonabant; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013045:Species Specificity; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D005971:Glutamates; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D017661:Receptors, Presynaptic; D050486:Serotonin Plasma Membrane Transport Proteins; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D012701:Serotonin; D000077285:Rimonabant