• Citer

Presynaptic CB1 cannabinoid receptors control frontocortical serotonin and glutamate release - Species differences

par Ferreira, Samira S.G.;Teixeira, Filipe F.M.;Garção, Pedro;Agostinho, Paula;Ledent, Catherine ;Cortes, Luísa;Mackie, Ken;Köfalvi, Attila
Référence Neurochemistry international, 61, 2, page (219-226)
Publication Publié, 2012-07

Article révisé par les pairs

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

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 CB1 cannabinoid receptor (CB 1R) 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. CB1R activation by the synthetic agonists, WIN55212-2 (1 μM) and R-methanandamide (1 μM) inhibited the simultaneously measured evoked Ca2+-dependent release of [14C]glutamate and [ 3H]serotonin from frontocortical nerve terminals of Wistar rats, in a fashion sensitive to the CB1R antagonists, O-2050 (1 μM) and LY320135 (5 μM). CB1R agonists also inhibited the evoked release of [14C]glutamate in C57BL/6J mice in a reversible fashion upon washout. Interestingly, the evoked release of [14C]glutamate and [3H]serotonin was significantly greater in the CB1R knockout CD-1 mice. Furthermore, CB1R binding experiments revealed similar frontocortical CB1R density in the rat and the CD-1 mouse. Still, the evoked release of [3H]serotonin was modulated by neither CB1R agonists nor antagonists in wild-type CD-1 or C57BL/6J mice. Altogether, this is the first study to demonstrate functional presynaptic CB1Rs in frontocortical glutamatergic and serotonergic terminals, revealing species differences. © 2012 Elsevier Ltd. All rights reserved.