The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum

Striatal slices were continuously superfused with L-3,5-3H-Tyrosine(50μCi/ml) and 3H-H2O [index of 3H-dopamine (3H-DA) synthesis] and 3H-DA estimated in 0.5 ml (2.5min) superfusate fractions. Depolarization with 50 mM k+ for 7.5 min induced a marked increase in 3H-DA release and a biphasic effect on synthesis. The decrease in the rate of 3H-H2O formation induced by K+ was not related to modifications of the specific activity of tyrosine in tissues. The possibility that the inhibition of synthesis was due to alterations in DA concentration in the synaptic cleft was examined. On the other hand, when the powerful neuroleptic fluphenazine was added to the superfusion medium in a concentration which only weakly blocked 3H-DA uptake (10-6M) it potentiated 3H-DA release and prevented the inhibition of synthesis both in the absence or presence of benztropine. The DA inhibitory effect on synthesis was still observed in the presence of benztropine (10-6M) while the NA effect was prevented. This concentration of benztropine blocked both DA and NA uptake. The administration of fluphenazine (10-6M) significantly prevented the decrease in 3H-DA synthesis induced by exogenous DA and partially prevented the effect of NA. The present results provide direct support for the concept that activation of presynaptic DA receptors located on DA terminals in the striatum of the rat results in an inhibition of synthesis and release of the transmitter. (orig.)