Toosendanin-induced change of dopamine level detected by microdialysis in vivo at rat striatum

To investigate the effect on central nervous transmission of toosendanin (T SN), a presynaptic blocker, rat striatum was perfused in vivo with a TSN-co ntaining artificial cerebrospinal fluid (ACSF) and the level of dopamine (D A) as well as related metabolites in the collected dialysates has been dete rmined by a microbore HPLC with electrochemical detection (microbore HPLC-E CD). The results are as follows: ( i) TSN induced a biphasic change of DA f rom its basal level;( ii) the basal contents of two metabolites, 3,4-dihydr oxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased in turn and stayed at a higher level than basal control for a long period. The basa l level of 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of 5-hydroxytr yptamine(5-HT), had a change similar to that of HVA; ( iii) after perfusion with TSN-containing ACSF, high K+-evoked DA release was inhibited. These r esults show that TSN does not selectively affect acetylcholine (ACh) releas e, but probably acts on a common mechanism responsible for transmitter rele ase at different synapses by interfering with the proteins involved in fusi on and resulting in diffusion of the vesicular contents into the cytoplasm and blockade of normal exocytosis.