Autoreceptors mediate the inhibition of dopamine synthesis by bromocriptine and lisuride in rats

The administration of bromocriptine and lisuride to rats caused a decrease in striatal dopamine (DA) synthesis, as measured by 3,4-dihydroxy-phenylalanine (DOPA) accumulation after decarboxylase inhibition. DOPA formation was inhibited by a maximum of about 60% of control values by bromocriptine and lisuride, 5.0 and 0.3 mg/kg, respectively. Both compounds showed very similar time-courses for the effect and failed to modify DOPA accumulation during the first 30 min. Pretreatment with (-)-sulpiride (50 mg/kg i.p.), a specific D2-receptor blocker, completely prevented the inhibitory effect of bromocriptine and lisuride on DOPA accumulation. Finally, both compounds significantly reversed the gamma-butyrolactone (GBL) (700 mg/kg i.p.)-induced DOPA accumulation at doses (0.25 and 0.015 mg/kg, respectively) that were inactive in normal rats. The data suggest that bromocriptine and lisuride act as agonists on D2-presynaptic autoreceptors which have different sensitivity to the agonist according to the basal firing rate of DA neurons.