Changes in cannabinoid CB1 receptors in striatal and cortical regions of rats with experimental allergic encephalomyelitis, an animal model of multiple sclerosis

Data, initially anecdotal, but recently supported on more solid experimenta l evidence, suggest that cannabinoids might be beneficial in the treatment of some of the symptoms of multiple sclerosis (MS). Despite this evidence, there are no data on the possible changes in cannabinoid CB1 or CB2 recepto rs, the main molecular targets for the action of cannabinoids, either in th e postmortem brain of patients with MS or in animal models of this disease. The present study addressed this question using the model of experimental allergic encephalomyelitis (EAE) in Lewis rats generated by inoculation of guinea pig myelin basic protein in Freund's adjuvant. After inoculation, an imals were examined daily to detect the appearance of neurological signs. T he first signs appeared around day 10 after inoculation, reaching the highe st degree by day 13, when animals were sacrificed and their brains removed and used for analysis of CB1 receptor binding, mRNA levels, and activation of GTP-binding proteins. CB1 receptor binding and mRNA levels were not affe cted in EAE rats in brain areas such as the hippocampus, limbic structures, and cerebellum. However, there was a marked decrease in both parameters in the caudate-putamen, both in the lateral and medial parts, although this d ecrease did not correspond with decreases in binding in the nuclei recipien t of striatal output neurons, which suggests that changes in CB1 receptors are exclusively located in the cell bodies of striatal neurons. In addition , CB1 receptor binding, but not mRNA levels, also decreased in the cerebral cortex, both in the deep and the superficial layers. The analysis of [S-35 ]GTP gammaS binding after activation of CB1 receptors with WIN55,212-2, a s ynthetic agonist, revealed that, despite the decrease in the number of CB1 receptors in EAE rats, these were more efficiently coupled to GTP-binding p rotein-mediated signaling mechanisms in both the caudate-putamen and the ce rebral cortex of these animals. In summary, these data suggest that the gen eration of EAE in Lewis rats would be associated with changes in CB1 recept ors in striatal and cortical neurons, which might be related to the allevia tion of some motor signs observed after the treatment with cannabinoid rece ptor agonists in similar models of MS in rodents. Synapse 41:195-202, 2001. (C) 2001 Wiley-Liss, Inc.