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

To investigate the effect on central nervous transmission of toosendanin (TSN), a presynaptic blocker, rat striatum was perfused in vivo with a TSN-containing artificial cerebrospinal fluid (ACSF) and the level of dopamine (DA) as well as related metabolites in the collected dialysates has been determined by a microbore HPLC with electrochemical detection (microbore HPLC-ECD). The results are as follows: ( i) TSN induced a biphasic change of DA from its basal level;( ii) the basal contents of two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased in turn and stayed at a higher level than basal control for a long period. The basal level of 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of 5-hydroxytryptamine(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 results show that TSN does not selectively affect acetylcholine (ACh) release, but probably acts on a common mechanism responsible for transmitter release at different synapses by interfering with the proteins involved in fusion and resulting in diffusion of the vesicular contents into the cytoplasm and blockade of normal exocytosis.