MiCaBra adresses the physiological and pharmacological roles of mitochondria-associated type-1 cannabinoid receptors in the brain (mtCB1). As a G Protein-Coupled Receptor, CB1 is mainly located on the plasma membrane of cells (pmCB1, neurons, astrocytes and others), where it mediates communication between the exterior and the interior of the cell itself. However, some years ago, we discovered that CB1 receptors are also functionally present inside cells, particularly in close association with important iintracellular organs like mitochondria. Here, previous studies from my lab showed that mtCB1 receptors control mitochondrial oxygen consumption and mediate cannabinoid-induced amnesic effects in a novel object recogtnition task.
Thus, MiCaBra aims at detailing and deeply investigationg the potential roles of mtCB1 receptors, starting from a biochemical/cell biology point of view, up to addressing their behavioral implications.
Considering the importance of CB1 receptors as the main targets of the plant cannabis sativa and as the main effector of the phyisiological endocannabinoid system, understanding their different modes of action is very important not only to better understand the mechanisms of brain functions, but also towards the development of novel therapeutic approaches for different conditions. Indeed, cannabis and cannabinoids are endowed with very interesting therapeutic potentials (analgesia, antispasm, anxiolytic, etc), but a certain number important possible side effects (amnesia, psychotic-like reponses, addiction potential, etc) limit their use in clinical settings and constitute the danger associated with their recreational use. As you can see below, our studies started addressing these issues, by demonstratin, for instance, that antisocial cannabinoid-induced behavior is specifically due to mtCB1 in astrocytes of specific brain regions. Moreover, we were recently able to differentiate the impact of pmCB1 and mtCB1 in the same neuronal circuit.
