BUFOTENINE HAS A PARACHLOROAMPHETAMINE-LIKE ACTION ON THE STORAGE ANDRELEASE OF SEROTONIN IN RAT SPINAL-CORD SYNAPTOSOMES

During a recent evaluation of the abilities of 5HT(3) agents to modula te the release of [H-3]-5HT from superfused rat spinal cord synaptosom es, bufotenine was found to be capable of increasing basal neurotransm itter efflux via a mechanism which was sensitive to blockade of the ne uronal membrane transport carrier (Williams et al., 1992). The present study was undertaken to further characterize the action of bufotenine on 5HT neuronal function. Bufotenine-evoked release of [H-3]-5HT was found to be unaltered by the removal of Ca++ from the superfusion medi a. In addition, using reserpine pre-treated tissues, it was determined that bufotenine releases 5HT primarily from extravesicular sites. A d irect interaction of bufotenine with the neuronal membrane transport c arrier is suggested by the ability of bufotenine to interact with site s labelled by [H-3]-citalopram (K-i=356 +/- 31 nM). A carrier mediated mechanism of release is further suggested by a comparable potency in the drug's ability to promote release (EC(50)= 892 +/- 60 nM). Bufoten ine also weakly inhibited MAO activity. These results demonstrate that bufotenine has an action on 5HT neurons comparable to p-chloroampheta mine.