Autoradiographic characterization of α2C-adrenoceptors in the human striatum

Indirect experimental evidence suggests that drugs acting on the α2C‐adrenoceptor could be useful in the treatment of neuropsychiatric disorders such as depression and schizophrenia. In rodent brain, the highest levels of α2C‐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 α2‐adrenoceptor ligands, the localization of α2C‐adrenoceptors has remained unknown. Recently, a selective α2C‐adrenoceptor antagonist, JP‐1302, was characterized, and to assess the presence of α2C‐adrenoceptors in human brain, we performed competition binding in vitro receptor autoradiography with JP‐1302 and the α2‐adrenoceptor subtype nonselective antagonist [ethyl‐3H]RS79948‐197 on rat and human postmortem brain sections. In striatum of both species, JP‐1302 vs. [ethyl‐3H]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 α2‐adrenoceptors in striatum is of the α2C subtype, whereas non‐α2C‐adreocneptors predominate in cortex and cerebellum. Because the α2C‐adrenoceptor subtype distribution pattern appears to be conserved between rodents and humans, results obtained from studies on the role of the α2C‐adrenoceptor in rodent models of neuropsychiatric disorders may be relevant also for human diseases. Synapse 62:508–515, 2008. © 2008 Wiley‐Liss, Inc.