The effect of chronic administration of cannabinoids on the survival of G93A rats was next examined. Recent evidence suggests that ALS is a disease characterized by chronic inflammation. Moreover, CB2 receptors are up-regulated in the target cells of several neuroinflammatory diseases. The primary Ganetespib cost site of pathology in ALS patients is the spinal-cord, with participation of lower brain stem areas late in the illness process. In G93A rats, CB2 receptor mRNA is selectively up regulated in the back in a temporal pattern directly paralleling illness development. More over, increased mRNA levels are correlated with increased CB2 receptor protein levels in the spinal cords of end stage G93A rats. These results suggest that, just like other neuroinflammatory disorders, the different parts of the cannabinoid system are selectively altered inside the target structure related to ALS pathogenesis. In addition, low levels of both CB2 receptor mRNA and protein noticed in WT OE spinal cables described here come in agreement with recent studies demonstrating the presence of functional CB2 receptors in the CNS of mice. Drugs which trigger CB2 receptors, effectively enhance the outward indications of a few inflammatory diseases including abdominal hypermotility as a result of Retroperitoneal lymph node dissection multiple sclerosis, atherosclerosis, endotoxic shock and Alzheimer s infection. Recent in vitro studies show that CB2 receptors are up regulated in microglia in response to inflammatory stimuli and that CB2 agonists reduce microglial activation. In our study, we demonstrate that not only are CB2 receptors considerably up regulated in the spinal cords of characteristic G93A rats, they are also in a position to functionally encourage G proteins when activated by agonists. Specifically, we suggest that in the first stages of motor neuron degeneration, CB2 receptors and endocannabinoids are CTEP selectively up regulated in spinal microglia as a compensatory, protective measure to reduce inflammation. Contrary to the above hypothesis, it’s important to note that a minimum of one study has suggested that the CB2 particular agonist AM 1241 might behave as a protean agonist, showing villain, inverse agonist or partial agonist activity with regards to the assay and/or tissue examined. Furthermore, in our study, AM 1241 produced little to no stimulation of G proteins in symptomatic G93A spinal cord membranes. Although the absence of agonist activity described here might be the result of less than optimal experimental conditions, it is also possible that the beneficial effect of AM 1241 in this animal model might instead result from antagonism of CB2 receptor activation produced by the endogenous cannabinoid agonists 2 arachido noyl glycerol and/or anandamide, regarded as elevated in the spinal cords of systematic G93A rats.