Autoradiographic characterization of α 2C ‐adrenoceptors in the human striatum

Abstract Indirect experimental evidence suggests that drugs acting on the α 2C ‐adrenoceptor could be useful in the treatment of neuropsychiatric disorders such as depression and schizophrenia. In rodent brain, the highest levels of α 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 α 2 ‐adrenoceptor ligands, the localization of α 2C ‐adrenoceptors has remained unknown. Recently, a selective α 2C ‐adrenoceptor antagonist, JP‐1302, was characterized, and to assess the presence of α 2C ‐adrenoceptors in human brain, we performed competition binding in vitro receptor autoradiography with JP‐1302 and the α 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 α 2 ‐adrenoceptors in striatum is of the α 2C subtype, whereas non‐α 2C ‐adreocneptors predominate in cortex and cerebellum. Because the α 2C ‐adrenoceptor subtype distribution pattern appears to be conserved between rodents and humans, results obtained from studies on the role of the α 2C ‐adrenoceptor in rodent models of neuropsychiatric disorders may be relevant also for human diseases. Synapse 62:508–515, 2008. © 2008 Wiley‐Liss, Inc.