AUTORADIOGRAPHIC LOCALIZATION AND PHARMACOLOGICAL CHARACTERIZATION OF [H-3] TANDOSPIRONE BINDING-SITES IN THE RAT-BRAIN

The regional distribution and pharmacological properties of [H-3]tandospirone binding sites in the rat brain were investigated using quantitative autoradiography. [H-3]Tandospirone binding was notable high in the dentate gyrus and CA1 area of the hippocampus, lateral septum, entorhinal cortex, interpeduncular nucleus and dorsal raphe nucleus. The distribution profiles of [H-3]tandospirone binding sites significantly correlated with that of serotonin (5-HT)1A receptor identified using [H-3]8-OH-DPAT. In competitive binding studies, [H-3]tandospirone binding was inhibited by 5-HT, 8-OH-DPAT, pindolol, buspirone and N-(alpha,alpha,alpha-trifluoro-m-tolyl)-piperazine. The potencies of these ligands correlated with their affinities for 5-HT1A receptors. In addition, there was no significant difference in the dissociation constant of [H-3]tandospirone binding between the dentate gyrus, CA1 area, dorsal raphe nucleus, lateral septum and entorhinal cortex (about 10 nM) suggesting that [H-3]tandospirone binds to 5-HT1A receptors with same affinities in these brain structures. The distribution pattern of binding sites for [H-3]tandospirone was also compared with that of benzodiazepine receptors identified using [H-3]fludiazepam to find common effector sites for different types of anxiolytics. Some similarities were observed. It is evident in the hippocampal formation that an overlap of intense binding occurred. 5-HT1A receptors in the hippocampus may participate in the anxiolytic effects of tandospirone.