The distribution and abundance of specific binding sites (=95% of total) in sections of rat CNS, revealed by quantitative receptor radioautography and image analysis, indicated a very discrete localization. Highest binding values were observed in cortical layers (binding in layers 1 and 2> binding in layers 3-6), hippocampal formation, striatum, dorsal septum, reticular thalamic nucleus, cerebellar molecular layer, and spinal cord dorsal horn. At 1 nM, the values for specific binding were highest in the cortical layers 1 and 2 and lowest in the brainstem (=2.6 and 0.4 pmol/mg of protein, respectively). Ro 48-8587 is a potent and selective AMPA receptor antagonist with improved binding characteristics (higher affinity, selectivity, and specific binding) compared with those previously reported. Key Words: a-Amino-3-hydroxy-5-methylisoxazole-4-propionate-9-lmidazol-1 -yl-8-nitro-2,3, 5,6-tetrahydro- High-affinity a-aniino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors are ligand-gated cation channels for L-glutalnate, the major excitatory transmitter in the mammalian CNS. Their activation mediates fast transmission at glutamatergic synapses. The receptors, heterooligomeric proteins composed of the subunits G1uR1 -4 with flip and flop forms (Hollmann and Heinemann, 1994;Bettler and Mulle, 1995;Barnard, 1997), play key roles in CNS physiology and pathology. AMPA receptor subunits G1uR1 -4 are differentially regulated during ontogeny, and in adult rat brain they have only partially overlapping distributions (Keinanen et al

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