Biology session

It was previously shown, that the hypothalamus–hypophisis–adrenal-axis (HPA-axis) function is strongly controlled by the endocannabinoid system. Enhancement of anandamide signaling by the blockade of its degradation increased basal corticosterone levels, while it dampened corticosterone stress responses. In the present study, we investigated the effects of the JZL184-induced blockade of monoacilglycerol lipase (MAGL), the degrading enzyme of the other main endocannabinoid 2-arachidonoylglycerol (2-AG) on basal and stress-induced corticosterone levels in male CD1 mice. We found that the blockade of MAGL dramatically increased basal corticosterone levels without affecting stress responses. Since acute changes in corticosterone levels can affect behavior, JZL184 was administered concurrently with the corticosterone synthesis inhibitor metyrapone, to investigate the corticosteron dependence of the behavioral effects in the elevated-plus maze and the open-field tests. We found that the inhibition of corticosterone-synthesis abolished some effects of the MAGL blockade on anxiety-related behaviour, while the locomotion-enhancing effects of the compound were not affected. Summarizing our results, specific blockade of MAGL activity dramatically increased basal levels of corticosterone, while leaving stress-induced levels unaltered. It also enhanced locomotor activity in a corticosterone-synthesis independent manner and had anxiolytic effects at least partly dependent of corticosterone.