| pubmed-article:18435421 | pubmed:abstractText | Indirect experimental evidence suggests that drugs acting on the alpha(2C)-adrenoceptor could be useful in the treatment of neuropsychiatric disorders such as depression and schizophrenia. In rodent brain, the highest levels of alpha(2C)-adrenoceptors are found in the striatum, with lower levels in cerebral cortex and hippocampus. In human brain, because of the poor subtype-selectivity of the available alpha(2)-adrenoceptor ligands, the localization of alpha(2C)-adrenoceptors has remained unknown. Recently, a selective alpha(2C)-adrenoceptor antagonist, JP-1302, was characterized, and to assess the presence of alpha(2C)-adrenoceptors in human brain, we performed competition binding in vitro receptor autoradiography with JP-1302 and the alpha(2)-adrenoceptor subtype nonselective antagonist [ethyl-(3)H]RS79948-197 on rat and human postmortem brain sections. In striatum of both species, JP-1302 vs. [ethyl-(3)H]RS79948-197 competition binding was biphasic, identifying high- and low-affinity binding sites, whereas in cortex and cerebellum, only low-affinity binding sites were detected. The results indicate that a significant portion of the alpha(2)-adrenoceptors in striatum is of the alpha(2C) subtype, whereas non-alpha(2C)-adreocneptors predominate in cortex and cerebellum. Because the alpha(2C)-adrenoceptor subtype distribution pattern appears to be conserved between rodents and humans, results obtained from studies on the role of the alpha(2C)-adrenoceptor in rodent models of neuropsychiatric disorders may be relevant also for human diseases. | lld:pubmed |
