Presynaptic CB(1) cannabinoid receptors control frontocortical serotonin and glutamate release--species differences |
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Authors: | Ferreira Samira G Teixeira Filipe M Garção Pedro Agostinho Paula Ledent Catherine Cortes Luísa Mackie Ken Köfalvi Attila |
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Affiliation: | Center for Neuroscience and Cell Biology of Coimbra, Faculty of Medicine, University of Coimbra, 3004-517 Coimbra, Portugal. |
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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. |
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Keywords: | 2-AG, 2-arachidonoyl-glycerol 4-AP, 4-aminopyridine CB1R, cannabinoid receptor type 1 DMSO, dimethylsulfoxide FELASA, Federation for Laboratory Animal Science Associations HEPES, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid PB, phosphate buffer PBS, phosphate buffered saline RIPA, radioimmunoprecipitation assay SERT, serotonin transporter VGLUT1,2, vesicular glutamate transporter types 1 and 2 WIN, WIN55212-2 mesylate |
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