Acute administration of amphetamine: differential regulation of dopamine synthesis in dopamine projection fields

In order to study the inhibitory mechanisms regulating dopamine (DA) synthesis in vivo, the effect of amphetamine in the presence and absence of selective D1 and D2-DA receptor antagonists was examined in various brain regions. In response to amphetamine (3 mg/kg s.c.) administration, DA synthesis in the striatum, but not the nucleus accumbens or the medial prefrontal cortex, exhibited a biphasic response (increased followed by decreased). The D1 selective antagonist, SCH 23390 (0.5 mg/kg s.c., 60 min), modestly increased DA synthesis (30%) in the striatum but not in the nucleus accumbens or the prefrontal cortex. However, pretreatment with the D1 DA receptor antagonist did not prevent the amphetamine-induced elevation of striatal DA synthesis 45 min after amphetamine administration. The D2 selective antagonist, eticlopride (2 mg/kg s.c., 60 min), increased DA synthesis in both the striatum and the nucleus accumbens but not in the prefrontal cortex. Although amphetamine alone increased DA synthesis only in the striatum, in the presence of D2-DA receptor blockade, amphetamine increased DA synthesis in the striatum, the nucleus accumbens and the medial prefrontal cortex. The results support the hypothesis that DA synthesis is differentially regulated by distinct inhibitory mechanisms depending on the projection field. The apparent differences in regulatory mechanisms may allow selective alteration of DA synthesis in one particular projection field, while other areas remain unaffected.