Presynaptic inhibition of dopamine synthesis in rat striatum: effects of chronic dopamine depletion and receptor blockade.

These studies assessed the effects of dopamine (DA) depletion and receptor blockade on presynaptic inhibition of DA synthesis in the rat striatum. Chronic reserpine administration significantly decreased striatal DA levels but did not affect in vivo tyrosine hydroxylase activity, as determined by following dihydroxyphenylalanine (DOPA) accumulations. Both reserpine and haloperidol increased the sensitivity of presynaptic striatal DA response as determined by the ability of apomorphine (APO) to inhibit DOPA accumulation in NSD-1015-treated rats. The effect of concurrent administration of reserpine plus haloperidol on presynaptic response was additive. Additivity occurred at doses of reserpine and haloperidol which induced maximum sensitivity when administered singularly. The data suggest that increases in sensitivity of presynaptic DA response following DA depletion and receptor blockade are mediated by separate regulatory mechanisms.