Presynaptic CB1 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 CB1 cannabinoid receptor (CB1R) 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 microM) and R-methanandamide (1 microM) 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 (500 nM) and LY320135 (5 microM). 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 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.

Presynaptic TRPV1 vanilloid receptor function is age- but not CB1 cannabinoid receptor-dependent in the rodent forebrain

“…Similarly to our previous report (Ferreira et al, 2012), the evoked release of [ 3 H]serotonin (comparing the S 1 values) was 11.8 ± 3.9% greater (n = 6, p < 0.01) in the CB 1 R knockout (KO) mice (Figs. 4A).…”

“…4A). This with the above data indicate that CB 1 Rs are tonically negatively coupled to the release of serotonin and glutamate as both nerve terminal types are positive for specific CB 1 R immunoreactivity (Köfalvi et al, 2005;Häring et al, 2007;Ferreira et al, 2012).…”

“…Presynaptic metabotropic CB 1 cannabinoid receptors have long been known to modulate the release of amino acid and monoamine transmitters (Katona et al, 1999;Nakazi et al, 2000;Balázsa et al, 2008;Ferreira et al, 2012). The endocannabinoids, anandamide and NADA can activate the ionotropic TRPV 1 R besides the CB 1 R. Our aim was to investigate the little understood nature of presynaptic functional TRPV 1 Rs.…”

“…This preparation was obtained as previously described (Ferreira et al, 2009(Ferreira et al, , 2012. Briefly, the caudate-putamen region without the nucleus accumbens (hereafter simply: striatum) and the frontal cortices were quickly dissected out into 2 mL of ice-cold sucrose solution (0.32 M, containing 5 mM HEPES, pH 7.4).…”

The interactive role of CB1 receptors and L-type calcium channels in hippocampal long-term potentiation in rats

“…On the other hand, the cannabinoid system modulates presynaptic glutamate release (Ferreira et al, 2012).…”