Modulation of the exocytotic and carrier-mediated transmitter release by endogenous and exogenously added cannabinoids

• Applicant: Professor Dr. Eberhard Schlicker
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2008 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 42860621

Cannabinoid CB1 receptors inhibit the action potential-driven, exocytotic transmitter release in neurons. Rimonabant, an inverse CB1 agonist, facilitates transmitter release, probably due to interruption of an endogenous tone built up by endocannabinoids like anandamide and/or 2-arachidonoylglycerol. Their role shall be clarified by determination of transmitter release in hippocampal slices (i) exposed to inhibitors of the synthesis and degradation of either endocannabinoid or (ii) obtained from mice not expressing such enzymes. The facilitatory effect of rimonabant might also be due to the fact that the CB1 receptors are constitutively active. This shall be checked by comparing the effect of an inverse agonist and neutral antagonist at CB1 receptors on transmitter release in isolated tissues and in cells. Finally, there is almost no information as to whether CB1 receptors affect the non-exocytotic glutamate release caused by hypoxia. The occurrence of such receptors and a possible endogenous tone shall be studied in hippocampal slices from wild type mice and mice not expressing CB1 receptors or endocannabinoid-synthesizing or -degrading enzymes. The findings may contribute to a better understanding of the clinical effect of rimonabant and of the possible use of CB1 agonists as neuroprotective drugs.

• DFG Programme: Research Units
• Subproject of: FOR 926: Physiology and Pathophysiology of the Endocannabinoid System